BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.