Barkley Differential Diagnosis Practice
Exam Latest Exam Update 2026
Table of Contents
1. Introduction and Exam Overview
2. Section 1: Cardiovascular Differential Diagnosis (Questions
1-25)
3. Section 2: Respiratory Differential Diagnosis (Questions 26-
50)
4. Section 3: Neurological Differential Diagnosis (Questions
51-75)
5. Section 4: Endocrine & Metabolic Differential Diagnosis
(Questions 76-100)
6. Section 5: Psychiatric Differential Diagnosis (Questions 101-
125)
7. Section 6: Gastrointestinal & Genitourinary Differential
Diagnosis (Questions 126-150)
8. Section 7: Musculoskeletal & Rheumatologic Differential
Diagnosis (Questions 151-175)
9. Section 8: Multisystem & Complex Differential Diagnosis
(Questions 176-200)
10. Answer Key Summary with Rationales
Introduction and Exam Overview
The Barkley Differential Diagnosis Practice Exam is designed to
strengthen clinical reasoning and diagnostic decision-making
, skills essential for nurse practitioner practice. Differential
diagnosis is the process of differentiating between two or more
conditions that share similar signs and symptoms, and it is a
core competency tested on all NP certification examinations,
including ANCC and AANP boards.
Barkley & Associates offers a comprehensive 45-Hour
Differential Diagnosis Across the Life Span course that covers
differential diagnoses for the most common disorders
encountered by NPs in family, adult, pediatric, internal
medicine, and urgent care settings. The course emphasizes
identification of key features in formulating differential
diagnoses, case-specific diagnosis application, and first-line
management of common disorders.
Core domains tested include:
• Systematic approach to differential diagnosis
• Red flags and high-risk presentations
• Clinical differences in presentations across the lifespan
• Pharmacotherapeutic considerations
• Integration of history, physical exam, and diagnostic findings
This comprehensive practice exam contains 200 questions
covering differential diagnosis across all major body systems.
Each question includes the correct answer marked in italics with
a detailed rationale in bold.
Section 1: Cardiovascular Differential Diagnosis (Questions
1-25)
,1. A 58-year-old male presents with substernal chest pain
that radiates to the left arm, associated with diaphoresis
and nausea. The pain began 30 minutes ago and is
unrelieved by rest. Which diagnosis must be ruled out first?
A. Stable angina
B. Acute coronary syndrome
C. Pericarditis
D. Costochondritis
Correct Answer: B
Rationale: The presentation of substernal chest pain
radiating to the left arm with diaphoresis and nausea,
unrelieved by rest, is highly concerning for acute coronary
syndrome (ACS). Immediate ECG and troponin are required.
Stable angina is relieved by rest; pericarditis causes
pleuritic pain relieved by sitting forward; costochondritis is
reproducible with palpation.
2. A 72-year-old female presents with sudden-onset
dyspnea, pleuritic chest pain, and tachycardia 5 days after
total knee arthroplasty. Which diagnosis should be
suspected?
A. Pneumonia
B. Pulmonary embolism
C. Aortic dissection
D. Pericarditis
Correct Answer: B
Rationale: Recent orthopedic surgery, sudden dyspnea,
pleuritic chest pain, and tachycardia strongly suggest
, pulmonary embolism. CT pulmonary angiography is the
diagnostic test of choice.
3. A 45-year-old male presents with severe tearing chest
pain radiating to the back, with a blood pressure difference
of 30 mmHg between arms. Which diagnosis is most likely?
A. Myocardial infarction
B. Aortic dissection
C. Pulmonary embolism
D. Pericarditis
Correct Answer: B
Rationale: Severe tearing chest pain radiating to the back
with a blood pressure differential between arms is classic
for aortic dissection. CT angiography is diagnostic. This is a
surgical emergency.
4. A 60-year-old female presents with sharp chest pain that
worsens with inspiration and is relieved by sitting forward.
A friction rub is heard on auscultation. Which diagnosis is
most likely?
A. Myocardial infarction
B. Pericarditis
C. Pneumothorax
D. Pulmonary embolism
Correct Answer: B
Rationale: Pleuritic chest pain relieved by sitting forward
with a pericardial friction rub is characteristic of acute
pericarditis. ECG may show diffuse ST elevation.
Exam Latest Exam Update 2026
Table of Contents
1. Introduction and Exam Overview
2. Section 1: Cardiovascular Differential Diagnosis (Questions
1-25)
3. Section 2: Respiratory Differential Diagnosis (Questions 26-
50)
4. Section 3: Neurological Differential Diagnosis (Questions
51-75)
5. Section 4: Endocrine & Metabolic Differential Diagnosis
(Questions 76-100)
6. Section 5: Psychiatric Differential Diagnosis (Questions 101-
125)
7. Section 6: Gastrointestinal & Genitourinary Differential
Diagnosis (Questions 126-150)
8. Section 7: Musculoskeletal & Rheumatologic Differential
Diagnosis (Questions 151-175)
9. Section 8: Multisystem & Complex Differential Diagnosis
(Questions 176-200)
10. Answer Key Summary with Rationales
Introduction and Exam Overview
The Barkley Differential Diagnosis Practice Exam is designed to
strengthen clinical reasoning and diagnostic decision-making
, skills essential for nurse practitioner practice. Differential
diagnosis is the process of differentiating between two or more
conditions that share similar signs and symptoms, and it is a
core competency tested on all NP certification examinations,
including ANCC and AANP boards.
Barkley & Associates offers a comprehensive 45-Hour
Differential Diagnosis Across the Life Span course that covers
differential diagnoses for the most common disorders
encountered by NPs in family, adult, pediatric, internal
medicine, and urgent care settings. The course emphasizes
identification of key features in formulating differential
diagnoses, case-specific diagnosis application, and first-line
management of common disorders.
Core domains tested include:
• Systematic approach to differential diagnosis
• Red flags and high-risk presentations
• Clinical differences in presentations across the lifespan
• Pharmacotherapeutic considerations
• Integration of history, physical exam, and diagnostic findings
This comprehensive practice exam contains 200 questions
covering differential diagnosis across all major body systems.
Each question includes the correct answer marked in italics with
a detailed rationale in bold.
Section 1: Cardiovascular Differential Diagnosis (Questions
1-25)
,1. A 58-year-old male presents with substernal chest pain
that radiates to the left arm, associated with diaphoresis
and nausea. The pain began 30 minutes ago and is
unrelieved by rest. Which diagnosis must be ruled out first?
A. Stable angina
B. Acute coronary syndrome
C. Pericarditis
D. Costochondritis
Correct Answer: B
Rationale: The presentation of substernal chest pain
radiating to the left arm with diaphoresis and nausea,
unrelieved by rest, is highly concerning for acute coronary
syndrome (ACS). Immediate ECG and troponin are required.
Stable angina is relieved by rest; pericarditis causes
pleuritic pain relieved by sitting forward; costochondritis is
reproducible with palpation.
2. A 72-year-old female presents with sudden-onset
dyspnea, pleuritic chest pain, and tachycardia 5 days after
total knee arthroplasty. Which diagnosis should be
suspected?
A. Pneumonia
B. Pulmonary embolism
C. Aortic dissection
D. Pericarditis
Correct Answer: B
Rationale: Recent orthopedic surgery, sudden dyspnea,
pleuritic chest pain, and tachycardia strongly suggest
, pulmonary embolism. CT pulmonary angiography is the
diagnostic test of choice.
3. A 45-year-old male presents with severe tearing chest
pain radiating to the back, with a blood pressure difference
of 30 mmHg between arms. Which diagnosis is most likely?
A. Myocardial infarction
B. Aortic dissection
C. Pulmonary embolism
D. Pericarditis
Correct Answer: B
Rationale: Severe tearing chest pain radiating to the back
with a blood pressure differential between arms is classic
for aortic dissection. CT angiography is diagnostic. This is a
surgical emergency.
4. A 60-year-old female presents with sharp chest pain that
worsens with inspiration and is relieved by sitting forward.
A friction rub is heard on auscultation. Which diagnosis is
most likely?
A. Myocardial infarction
B. Pericarditis
C. Pneumothorax
D. Pulmonary embolism
Correct Answer: B
Rationale: Pleuritic chest pain relieved by sitting forward
with a pericardial friction rub is characteristic of acute
pericarditis. ECG may show diffuse ST elevation.