This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter. A double-blind, parallel, randomized, placebo-controlled protocol was used, and 6 large, urban hospitals, both university-affiliated and private, participated. The study involved 113 patients with atrial fibrillation or flutter, a ventricular rate ≥120 beats/min and systolic blood pressure ≥90 mm Hg without severe heart failure. The dose of intravenous diltiazem (or identical placebo) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective. If a patient did not respond, the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given. Of 56 patients, 42 (75%) randomized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg, for a total response rate of 52 of 56 patients (93%), whereas 7 of 57 patients (12%) responded to placebo (p < 0.001). After the double-blind protocol, 49 of the 57 patients who received placebo were then given diltiazem; 47 of 49 responded, for an overall response rate of 99 of 105 patients (94%) with diltiazem. The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes. Side effects occurred in 14 patients, 7 of whom had asymptomatic hypotension not requiring intervention. Thus, intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter. Blood pressure decreased slightly. Side effects were mild.