Background: This study is to determine the risk factors and outcome for post-pancreaticoduodenectomy bleeding, and to assess the roles of surgery and intravascular intervention in its management. Methods: Post-pancreaticoduodenectomy data of 628 patients were analyzed with regards to post-pancreaticoduodenectomy bleeding. Results: Post-pancreaticoduodenectomy bleeding occurred in 58 patients (9.2%) and led to death in 23 patients. Pancreatic leakage and intra-abdominal abscess were independent risk factors for both extraluminal and intraluminal post-pancreaticoduodenectomy bleeding. The most common source of bleeding was the gastroduodenal artery (n = 9, 24.3%), and 8 of these patients (88.9%) experienced gastroduodenal artery bleeding in late post-pancreaticoduodenectomy bleeding. Hemostasis for post-pancreaticoduodenectomy bleeding was achieved by surgery in 22 patients (78.6%) and intravascular intervention in 7 patients (58.3%). Transarterial embolization for gastroduodenal artery bleeding did not deteriorate liver function in most patients except for 1 who died of hepatic failure. Conclusions: The placement of metallic clips on the gastroduodenal artery stump during a pancreaticoduodenectomy is helpful in identifying overlooked intermittent sentinel bleeding during angiography. Transarterial embolization for gastroduodenal artery bleeding could not guarantee against hepatic failure. The intravascular placement of a covered stent is the preferred procedure to avoid the complete interruption of arterial blood supply to the liver.