Aim. To assess safety and clinical-economic effectiveness of complex postoperative rehabilitation after pancreatoduodenectomy. Material and methods. 73 patients were included in the study. Main group consisted of 39 patients who underwent accelerated postoperative rehabilitation that was developed in our clinic. In the control group of 34 patients this protocol was not applied. The main components of rehabilitation were multicomponent analgesia, early enteral nutrition, physical rehabilitation by using of exercise therapy and physiotherapy. Results. There were no significant differences in the incidence of postoperative complications and mortality (58.8% and 74.3%; p=0.213, 5.8% and 7.7%; p=0.678, respectively). Median of postoperative hospital-stay in the study group was 13 days (9; 16), in the control group — 15 days (9; 24). An estimated economic effect in the study group was 558 764, 84 rubles. Conclusion. Accelerated postoperative rehabilitation after pancreatoduodenectomy is safe and does not lead to increased number of postoperative complications and mortality. Developed protocol has clinical advantages and is cost-effective.