Introduction. Postoperative atrial fibrillation (POAF) is the most frequent complication after open heart surgery. In our previous experimental animal study of local epicardial amiodarone use, the technical ability and safety of the proposed method was demonstrated. Objective. To assess the safety and efficacy of local epicardial application of amiodarone-releasing hydrogel material in the prevention of POAF in patients after coronary artery bypass surgery (CABG). Material and methods. We performed an open-label randomized prospective clinical study. Patients were randomized in two groups: study group (n=30, with the application of amiodarone-releasing hydrogel), and control group (n=30, without application). The dose of amiodarone in hydrogel material was 60 mg for all patients (with dose calculation 1 mg/kg body weight). Heart rhythm control lasted for 5 days after surgery. Results. The research was completed according to the protocol. The study included 60 patients (47 male, 13 female), mean age of 62±8.5. Baseline clinical, laboratory and instrumental parameters in groups did not have significant differences. Intraoperative data did not have statistically significant differences too. The incidence of POAF development between two groups was statistically significant: in the study group, AF was diagnosed in one patient, which was 3.3%, while in the control group, the POAF frequency was 37%, (p<0.001). ECG analysis in 5 days revealed statistically significant difference of the P–Q intervals duration: in the study group the P–Q interval was 0.14 (0.12; 0.16) while in the control group P–Q duration was 0.12 (0.12; 0.14) (p=0.002). Significant changes between QRS and Q–T intervals were not detected. According to the Holter ECG monitoring data in 5 days, the average heart rate in the study group was 59 (52; 60) beats per min., while in control group 69 (65;75) beats per min., which was statistically significant (p<0.001). Minimum heart rate per day was also significantly different in two groups: in the study group minimum heart rate was 50 (49; 55) beats per min., vs. in the control group 55 (50; 58) beats per min., (p=0.008). The length of stay of patients in two groups was also different: 6 (6; 7) bed-days in study group vs. 8 (8; 9) days in control group (р<0.001). The risk of POAF incidences was calculated using the Cox regression model. Parameters with high intercorrelation (r>0.7) were excluded. Among all the clinical, laboratory and instrumental parameters, the age (p=0.009) and the procedure of amiodarone-releasing hydrogel applying (p=0.011) were statistically significant. Conclusion. The local epicardial amiodarone delivery by using of amiodarone-releasing hydrogel material is a safe option. There were no any cases of infection processes registered. Amiodarone-releasing (60 mg) hydrogel is an effective treatment for the prevention of postoperative AF in patients after coronary artery bypass graft surgery in comparison with control group (p<0.001). The age (p=0.009) and the procedure of amiodaronereleasing hydrogel applying (p=0.011) were statistically significant for POAF incidences development.