Introduction: Kussmaul's sign, the absence of a drop in JVP or a paradoxical increase in JVP on inspiration, can be elicited clinically as an indicator of right ventricular myocardial infarction (RVMI). RVMI poses unique diagnostic and management challenges. It complicates 30-50% of inferior MI and is associated with increased mortality when compared to inferior MI without RV involvement. Early recognition allows maintenance of preload by avoiding use of nitroglycerin, diuretic and narcotic medication, and treatment with fluids and vasopressors. We reviewed the evidence for Kussmaul's sign for diagnosis of RVMI. Methods: We conducted a librarian assisted search using PubMed, Medline, Embase, the Cochrane database, relevant conference abstracts from 1965 to October 2019. No restrictions for language or study type were imposed. All studies with patients presenting with acute myocardial infarction were reviewed. Two independent reviewers extracted data from relevant studies. Studies were combined when similar study populations were present. Study quality was assessed using the QUADAS-2 tool. Random effects meta-analysis was performed using metaprop in Stata for the 3 reference standards combined. Subset analysis for each of the 3 reference standards was completed. Results: We identified 122 studies: 10 were selected for full text review. Eight studies had comparable populations with a total of 469 consecutive patients admitted to the coronary care unit with acute inferior myocardial infarction and were included in the analysis. Prevalence of RVMI was 36% (CI 95% 31.8–40.5). References standards for the diagnosis of RVMI included echocardiography, 16 lead ECG and haemodynamic studies. A gold standard for diagnosis of RVMI is lacking and thus the reference standards were combined. Kussmaul's sign had a sensitivity of 69.3% (CI 95% 46.3 - 85.5, I2- 86.7%), specificity of 95.1% (CI 95% 75.6 - 99.2, I2- 89.3%) and LR + 14.1 (CI 95% 2.6-73.2). Subset analysis of echocardiography, ECG and haemodynamic studies revealed sensitivity of 45%, 77% and 82% (I2- 62%, N/A, 70%) respectively and specificity of 92%, 84% and 92% (I2- 86%, N/A, 86%). Conclusion: Kussmaul's sign is specific for acute right ventricular myocardial infarction and may serve as an important clinical sign of right ventricular dysfunction requiring preload preserving management.