Echocardiography is recommended for the detection of valvular regurgitation in asymptomatic users of anorexigens with a heart murmur. To determine the prevalence and diagnostic value of heart murmurs for valvular regurgitation, 223 patients receiving dexfenfluramine therapy for 6.9 months and 189 matched controls underwent history and cardiac auscultation by experienced noncardiologists unaware of echocardiography. Color Doppler echocardiograms were interpreted by 3 observers unaware of patients' clinical data. The frequency of at least mild regurgitation of any valve and abnormal regurgitation (moderate mitral or tricuspid or mild aortic regurgitation) were determined. Heart murmurs heard in 31 dexfenfluramine users (14%) and in 20 controls (11%) were all systolic and of grade I to II/VI intensity. Mild or worse regurgitation of any valve showed a trend in patients (18% vs 11.6% in controls, odds ratio [OR] 1.66, confidence interval [CI] 0.95 to 2.9, p = 0.08), but abnormal regurgitation (includes Food and Drug Administration grade regurgitation) was more common in patients (9% vs 3% in controls, OR 3.0, CI 1.18 to 7.65, p = 0.02). In dexfenfluramine users, heart murmurs were associated with at least mild or abnormal regurgitation (OR 3.1 and 3.05, 95% CI 1.34 to 7.13 and 1.1 to 8.67; p = 0.008 and 0.036, respectively), had a specificity of 89% and 88%, negative predictive value of 85% and 93%, but sensitivity of 37% and 30%, and positive predictive value of 35% and 19%, respectively. Most valves missed by cardiac auscultation had normal morphology and mild regurgitation. Finally, heart murmurs had better diagnostic value for either type of valvular regurgitation than heart murmurs and clinical variables or clinical variables alone. In summary, in dexfenfluramine users the prevalence of heart murmurs was low and their absence predicted absence of mild or worse regurgitation of any valve or abnormal valvular regurgitation. Therefore, cardiac auscultation should be the screening method of choice for detecting valvular regurgitation in users of anorexigens.