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Objectives This randomized study was designed to compare the safety and efficacy of intravenous diltiazem versus intravenous cedilanid-D (deslanoside) for ventricular rate control in patients with atrial fibrillation (AF). Analysis of the effect on conduction system of these drugs was also performed.Methods Forty three patients with AF were randomly assigned to receive intravenous therapy with 0.25mg/kg diltiazem (n= 21) or 0.4mg cedilanid-D (n= 22). If not effective at 120 minutes (＜ 20% decrease in pretreatment ventricular rate or can not convert to sinus rhythm= another dose of diltiazem or 0.2mg cedilanid-D was administered. Blood pressure and electrocardiographic recordings were performed before and after 5,10, 20, 30, 60 minutes of drug administration. Further recordings were performed at 120 minutes in noneffective patients, and at 180 minutes in patients who received second time drug administration. To evaluate the effect on conduction system of these two drugs by measuring PA, AH and HV intervals using His bundle electrogram test another nineteen sinus rhythm patients were randomized to diltiazem (n=9) and cedilanid (n=10) group. His bundle electrogram recordings were performed before and after 5, 10, 20 and 30 minutes of drug administration. Statistical significance was assessed with the use of t test, Fisher’s exact test, ANOVA and LSD methodology. Results At baseline and after 5,10, 20, 30, 60 minutes of drug administration the heart rates (mean±SD) were(133±15), (92±20), (87±22), (85 ±20), (85 ±21), (85 ±23)beats/minute in diltiazem group respectively and( 140±21 ), ( 122±24),(118±25), (110±26), (112±25), (110±28) beats/minute in cedilanid-D group respectively. Heart rate reduction was higher in diltiazem group than cedilanid group during 5 (41±20 vs 17±14,P ＜ 0.01); 10(46±21 vs 22±20, P＜0.01); 20 (48±21 vs 29±22,P＜0.01 ); 30(48±22 vs 27±22, P＜0.01 ) and 60 minutes (48±23 vs 29±24, P＜ 0.05). Both drugs had no effect on both systolic and diastolic blood pressure (P ＞0.05)and no major side effects were noticed. Diltiazem maintained effective ventricular rate in 20 patients,whereas cedilanid-D maintained in 15 patients within 180 minutes (95.2%vs 68.2%,P＜ 0.05). There were no statistical significance in baseline heart rate, age and weight between the two groups. Both diltiazem and cedilanid-D can increase AH interval, but have no effect on HV and PA intervals in sinus rhythm patients.Conclusions Both diltiazem and cedilanid-D decrease ventricular heart rate, but heart rate reduction is significantly higher in diltiazem group, thus should be considered as a drug of choice for emergency control of ventricular rate. Under clinical monitoring this dose of diltiazem seems to be safe and applicable in AF patients with congestive heart failure. Both drugs have no effect on PA and HV intervals but increase the AH interval thereby can reduce ventricular rate.