Eight hundred twelve men with presumed acute myocardial infarction and left ventricular filling pressure of at least 12 mm Hg participated in a randomized double-blind placebo-controlled trial to assess the efficacy of a 48-hour infusion of sodium nitroprusside. The mortality rates at 21 days (10.4 per cent in the placebo group and 11.5 per cent in the nitroprusside group) and at 13 weeks (19.0 per cent and 17.0 per cent, respectively) were not significantly affected by treatment. The efficacy of nitroprusside was related to the time of treatment: the drug had a deleterious effect in patients whose infusions were started within nine hours of the onset of pain (mortality at 13 weeks, 24.2 per cent vs. 12.7 per cent; P = 0.025) and a beneficial effect in those whose infusions were begun later (mortality at 13 weeks, 14.4 per cent vs. 22.3 per cent; P = 0.04). Nitroprusside should probably not be used routinely in patients with high left ventricular filling pressures after acute myocardial infarction. However, the results in the patients given late treatment suggest that those with persistent pump failure might receive sustained benefit from short-term nitroprusside therapy. (N Engl J Med. 1982; 306:1129–35.) ACUTE myocardial infarction is frequently accompanied by global dysfunction of the left ventricle and continuing ischemia.1 2 3 In recent years recognition of the dynamic nature of this syndrome and the evidence that pharmacologic and physiologic manipulations can acutely alter the function and perfusion of the left ventricle4 5 6 has led to the hope that drug interventions can alter the natural history of the disease. Infusion of sodium nitroprusside, a potent arterial and venous dilator, has acutely improved left ventricular pump function in both experimental7,8 and clinical9 10 11 myocardial infarction by raising cardiac output and reducing filling pressure. The salutary clinical and hemodynamic response.