To present a retrospective post-pancreaticoduodenectomy case series that had sentinel bleeding after pancreaticoduodenectomy and to evaluate the necessity and safety of prophylactic embolization. Fifteen post-pancreaticoduodenectomy patients with sentinel bleeding after pancreaticoduodenectomy were included in this study. Digital subtraction angiography was performed 6 hours after sentinel bleeding was detected; 8 patients received a prophylactic embolization, while 7 patients received digital subtraction angiography only. If a delayed massive hemorrhage occurred, intensive treatment such as a laparotomy or Transcatheter Angiographic Embolization (TAE) was performed. Fourteen (93.3%) patients’ angiographic findings were negative, and 1 patient had a pseudoaneurysm. All 8 prophylactic embolization patients were alive, and no delayed massive hemorrhage occurred. The delayed massive hemorrhage incidence with digital subtraction angiography was 42.8% (3 of 7), and 1 patient (14.3%) died because of a delayed massive hemorrhage. Compared with digital subtraction angiography, length of stay (p=0.048) and transfusion rates (p=0.002) decreased markedly in prophylactic embolization group. No serious complications related to prophylactic embolization were observed. Prophylactic embolization should be the treatment of choice for post-pancreaticoduodenectomy patients with sentinel bleeding, because it is safe and could reduce the postoperative length of stay and transfusion rate.