Impaired left ventricular function after acute myocardial infarction (AMI) is associated with an increased risk of death. Despite recent advances in the management of these patients, sudden death accounts for up to 50% of this mortality, and effective treatment strategies have yet to be identified. Preliminary trials with amiodarone have offered promise that drugs that prolong action potential duration by blocking the potassium channel may be useful in reducing this mortality. The Survival With Oral d-Sotalol (SWORD) trial is a multicenter, multinational study which tests the hypothesis that the class III agent d-sotalol will reduce all-cause mortality in high-risk survivors of AMI. The trial will enroll 6,400 patients with left ventricular dysfunction (ejection fraction < or = 40%) and a recent (6 to 42 days) or a remote (> 42 days) AMI with overt heart failure (New York Heart Association class II or III). In approximately 500 centers throughout the world, men and women aged > or = 18 years will be enrolled and randomized to placebo or d-sotalol (200 mg/day). The minimal follow-up will be 18 months. The trial has a 90% power to detect a 20% reduction in all-cause mortality. The rationale, design, and trial methods are described.