Objectives: To evaluate the safety in terms of hypotensive action of nitroglycerin and lisinopril started early after myocardial infarction. Patients and Methods: One thousand five hundred twenty-six patients with suspected myocardial infarction were randomized by 174 centers within 24 hours from the onset of symptoms to receive oral lisinopril (5 then 10 mg/day), nitroglycerin (intravenous infusion during the first 24 hours, then 10 mg/day transdermal), or neither. Results: Systolic blood pressure, intensively monitored during the first 72 hours, decreased sharply by 11 mm Hg during the first 2 hours, then more slowly to an average value of 120 mm Hg. Nitroglycerin lowered systolic blood pressure during the first 24 hours by 2.7 mm Hg versus control subjects, and it was similar to control subjects from 24 hours. Lisinopril reduced systolic blood pressure by 4.2 mm Hg over 72 hours compared with control subjects. Persistent hypotension was significantly more frequent in the Lisinopril group (21.4%) than in the nitroglycerin group (10.9%) or control group (9.8%), but absolute numbers of deaths in patients with persistent hypotension were almost identical. Conclusions: Lisinopril and nitroglycerin are both safe and effective in reducing blood pressure in the first day after myocardial infarction. However, the effect is lost thereafter with transdermal nitroglycerin, but persists with lisinopril.