OBJECTIVE To compare the effects of i.v. diltiazem and i.v. digoxin on ventricular rate control in the emergency treatment of acute atrial fibrillation and flutter (AFF). METHODS This prospective, randomized, open-label trial involved 30 consecutive patients who presented with acute AFF to the emergency department of an urban, 420-bed community teaching hospital from April 1993 through March 1994. Exclusion criteria included systolic blood pressure lower than 100 mm Hg, treatment with calcium-channel blockers other than diltiazem, lack of informed consent, and objection of the private physician. Patients were randomly assigned to receive either i.v. diltiazem alone, i.v. digoxin alone, or both. Heart rate control was defined as a ventricular rate of less than 100 beats/minute. I.v. digoxin, 25 mg, was given as a bolus at time 0 and at time 30 minutes. An initial dose of .25 mg/kg diltiazem was given intravenously over the first 2 minutes, followed by a dose of .35 mg/kg at time 15 minutes and then a titratable i.v. infusion at a rate of 10 to 20 mg/hour to maintain heart rate control. The dosing regimens were the same whether the drugs were given alone or in combination. Heart rhythm, heart rate, and blood pressure were measured at time 0, 5, 10, 15, 30, 60, 120, and 180 minutes. Statistical significance was assessed with the use of Student's t test and ANOVA methodology. RESULTS At time 0, the heart rate (mean +/- SD) was 150 +/- 19 beats/minute in the diltiazem group and 144 +/- 12 in the digoxin group (difference not significant, P = .432). The decrease in heart rate from time 0 reached statistical significance at time 5 minutes in the diltiazem group (P = .0006); the mean rates at time 5 minutes were 111 +/- 26 beats/minute for diltiazem and 144 +/- 13 for digoxin. The decrease in heart rate achieved with digoxin did not reach statistical significance until time 180 minutes (P = .0099), at which time the rates were 90 +/- 13 for diltiazem and 117 +/- 22 for digoxin. CONCLUSIONS Treatment of acute AFF with i.v. diltiazem decreases ventricular heart rate significantly within 5 minutes, compared with 3 hours for treatment with i.v. digoxin. No advantage was noted within 3 hours for i.v. treatment with a combination of diltiazem and digoxin. I.v. diltiazem is superior to i.v. digoxin in the emergency control of ventricular rate in acute AFF and should be considered as a drug of choice for this condition. This study was not large enough to adequately assess adverse effects, and further studies may be warranted for clinical validation.