Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain. The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infarction (MI) in a randomized, controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis. First MI survivors were randomized to a low-fat (n = 50) or Mediterranean-style (n = 51) diet. The 2 diets were low in saturated fat (< or =7% kcal) and cholesterol (< or =200 mg/day); the Mediterranean-style diet was distinguished by greater omega-3 fat intake (>0.75% kcal). Participants received individual dietary counseling sessions, 2 within the first month and again at 3, 6, 12, 18, and 24 months, along with 6 group sessions. Combined dietary intervention groups (cases, n = 101) were compared with a usual-care group (controls, n = 101) matched for age, gender, MI type and treatment, and status of diabetes mellitus and hypertension. Primary-outcome-free survival (a composite of all-cause and cardiac deaths, MI, hospital admissions for heart failure, unstable angina pectoris, or stroke) did not differ between low-fat (42 of 50) and Mediterranean-style (43 of 51) diet groups over a median follow-up period of 46 months (range 18 to 72; log-rank p = 0.81). Patients receiving dietary intervention had better primary-outcome-free survival (85 of 101) than usual-care controls (61 of 101) (log-rank p <0.001), with unadjusted and adjusted odds ratios of 0.33 (95% confidence interval 0.18 to 0.60, p <0.001) and 0.28 (95% confidence interval 0.13 to 0.63, p = 0.002), respectively. In conclusion, active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI.