Objectives: To examine the impact of prognostic factors on the outcome of treatment with warfarin or aspirin after acute myocardial infarction. Methods: Patients from the Warfarin Aspirin Re-Infarction Study, assigned to treatment with warfarin (n = 1,216) or aspirin (n = 1,206) after myocardial infarction, were stratified according to important prognostic factors. Survival from the composite endpoint of death, myocardial infarction and thromboembolic stroke was estimated within each stratum by odds ratios (OR). The effect of therapy was then tested for heterogeneity across the two groups. Unadjusted analyses were complemented with regression analyses. Results: In diabetics the OR was 1.54 (95% CI 0.80–2.94) compared to 0.75 (95% CI 0.60–0.93) in nondiabetic patients. The latter difference was statistically significant when testing for heterogeneity, suggesting effect modification of warfarin by diabetes. After adjusting for confounders, diabetic patients who received warfarin had a 56% excess risk of an endpoint as compared with those receiving aspirin. By contrast, nondiabetic patients on warfarin had a 22% lower risk of an endpoint than those allocated to aspirin. Conclusions: The present data suggest less benefit from warfarin as compared to aspirin in diabetics. The mechanisms behind this remain in question.