The Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) study demonstrated a significant increase in myocardial infarction events with dabigatran compared with warfarin, provoking renewed interest in whether vitamin K antagonists are useful drugs for the prevention of myocardial infarction in high-risk patients with atrial fibrillation. Present analyses examined whether there was an increased risk of myocardial infarction associated with non-warfarin anticoagulants (Stroke Prevention with the ORal direct Thrombin Inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial Fibrillation III and IV, RE-LY, Amadeus) or "anticoagulant equivalents" (Atrial fibrillation Clopidogrel Trial with Irbesartan for the prevention of Vascular Events) in patients with atrial fibrillation who are prescribed anticoagulation for stroke thromboprophylaxis. The overall annual event rate for those receiving warfarin was 0.98% compared with 1.32% for those receiving comparators. Warfarin was associated with a significant reduction in myocardial infarction (relative risk 0.77; 95% confidence interval (CI), 0.63-0.95), an effect largely driven by the RE-LY trial. Sensitivity analyses, excluding RE-LY, revealed a nonsignificant reduction in myocardial infarctions (relative risk 0.83; 95% CI, 0.62-1.10); an analogous analysis excluding the Atrial fibrillation Clopidogrel Trial with Irbesartan for the prevention of Vascular Events demonstrated a significant reduction in myocardial infarctions (relative risk 0.80; 95% CI, 0.64-1.00). Warfarin might provide a protective effect against myocardial infarction compared with non-warfarin anticoagulants or "anticoagulation equivalents" in patients with atrial fibrillation who are prescribed anticoagulation for stroke thromboprophylaxis.