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To compare the clinical efficacy of intravenous diltiazem, digoxin, and amiodarone for acute ventricular rate (VR) control in patients with acute symptomatic atrial fibrillation (AF) necessitating hospitalization.Randomized control trial.Acute emergency medical admission unit in a regional teaching hospital in Hong Kong.One hundred fifty adult patients with acute AF and rapid VR (>120 bpm).Patients were randomly assigned in 1:1:1 ratio to receive intravenous diltiazem, digoxin, or amiodarone for VR control.The primary end point was sustained VR control (<90 bpm) within 24 hours; the secondary end points included AF symptom improvement and length of hospitalization. At 24 hours, VR control was achieved in 119 of 150 patients (79%). The time to VR control was significantly shorter among patients in the diltiazem group (log-rank test, p < 0.0001) with the percentage of patients who achieved VR control being higher in the diltiazem group (90%) than the digoxin group (74%) and the amiodarone group (74%). The median time to VR control was significantly shorter in the diltiazem group (3 hours, 1–21 hours) compared with the digoxin (6 hours, 3–15 hours, p < 0.001) and amiodarone groups (7 hours, 1–18 hours, p = 0.003). Furthermore, patients in the diltiazem group persistently had the lowest mean VR after the first hour of drug administration compared with the other two groups (p < 0.05). The diltiazem group had the largest reduction in AF symptom frequency score and severity score (p < 0.0001). In addition, length of hospital stay was significantly shorter in the diltiazem group (3.9 ± 1.6 days) compared with digoxin (4.7 ± 2.1 days, p = 0.023) and amiodarone groups (4.7 ± 2.2 days, p = 0.038).As compared with digoxin and amiodarone, intravenous diltiazem was safe and effective in achieving VR control to improve symptoms and to reduce hospital stay in patients with acute AF.