OBJECTIVE-We carried out a secondary analysis in high-risk patients with a previous myocardial infarction (MI) and diabetes in the Alpha Omega Trial. We tested the hypothesis that in these patients an increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA) will reduce the incidence of ventricular arrhythmias and fatal MI. RESEARCH DESIGN AND METHODS-A subgroup of 1,014 post-MI patients with diabetes aged 60-80 years was randomly allocated to receive one of four trial margarines, three with an additional amount of n-3 fatty acids and one placebo for 40 months. The end points were ventricular arrhythmia related events and fatal MI. The data were analyzed according to the intention-to-treat principle, using multivariable Cox proportional hazards models. RESULTS-The patients consumed on average 18.6 g of margarine per day, which resulted in an additional intake of 223 mg EPA plus 149 mg DHA and/or 1.9 g ALA in the active treatment groups. During follow-up, 29 patients developed a ventricular arrhythmia related events and 27 had a fatal MI. Compared with placebo patients, the EPA-DHA plus ALA group experienced less ventricular arrhythmia related events (hazard ratio 0.16; 95% Cl 0.04-0.69). These n-3 fatty acids also reduced the combined end-point ventricular arrhythmia related events and fatal MI (0.28; 0.11-0.71). CONCLUSIONS-Our results suggest that low-dose supplementation of n-3 fatty acids exerts a protective effect against ventricular arrhythmia related events in post-MI patients with diabetes.