Background: After case reports of cardiac-valve abnormalities related to the use of appetite suppressants were published, we undertook a study to determine the prevalence of the problem using transthoracic echocardiography. Methods: We examined patients who had taken dexfenfluramine alone, dexfenfluramine and phentermine, or fenfluramine and phentermine for various periods. We enrolled obese patients who had taken or were taking these agents during open-label trials from January 1994 through August 1997. We also recruited subjects who had not taken appetite suppressants and who were matched to the patients for sex, height, and pretreatment age and body-mass index. The presence of cardiac-valve abnormalities, defined by the Food and Drug Administration and Centers for Disease Control and Prevention as at least mild aortic-valve or moderate mitral-vale insufficiency, was determined independently by at least two cardiologists. Multivariate logistic-regression analysis was used to identify factors associated with cardiac-valve abnormalities. Results: Echocardiograms were available for 257 patients and 239 control subjects. The association between the use of any appetite suppressant and cardiac-valve abnormalities was analyzed in a final matched group of 233 pairs of patients and controls. A total of 1.3 percent of the controls (3 of 233) and 22.7 percent of the patients (53 of 233) met the case definition for cardiac-valve abnormalities (odds ratio, 22.6; 95 percent confidence interval, 7.1 to 114.2; P<0.001). The odds ratio for such cardiac- valve abnormalities was 12.7 (95 percent confidence interval, 2.9 to 56.4) with the use of dexfenfluramine alone, 24.5 (5.9 to 102.2) with the use of dexfenfluramine and phentermine, and 26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine. Conclusions: Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.