Post-endoscopic sphincterotomy bleeding is a common complication of biliary sphincterotomy, and the incidence varies from 1% to 48%. It can be challenging to localize the bleeder or to administer various interventions through a side-viewing endoscope. This study aimed to evaluate the risk factors of post-endoscopic sphincterotomy bleeding and the outcome of endoscopic intervention therapies. We retrospectively reviewed the records of 513 patients who underwent biliary sphincterotomy in Mackay Memorial Hospital between 2011 and 2016. The blood biochemistry, comorbidities, indication for sphincterotomy, severity of bleeding, endoscopic features of bleeder, and type of endoscopic therapy were analyzed. Post-endoscopic sphincterotomy bleeding occurred in 65 (12.6%) patients. Forty-five patients had immediate bleeding and 20 patients had delayed bleeding. The multivariate analysis of risk factors associated with post-endoscopic sphincterotomy bleeding were liver cirrhosis (P = 0.029), end-stage renal disease (P = 0.038), previous antiplatelet drug use (P<0.001), and duodenal ulcer (P = 0.023). The complications of pancreatitis and cholangitis were higher in the bleeding group, with statistical significance. Delayed bleeding occurred within 1 to 7 days (mean, 2.5 days), and 60% (12/20) of the patients received endoscopic evaluation. In the delayed bleeding group, the successful hemostasis rate was 71.4% (5/7), and 65% (13/20) of the patients had ceased bleeding without endoscopic hemostasis therapy. Comparison of different therapeutic modalities showed that cholangitis was higher in patients who received epinephrine spray (P = 0.042) and pancreatitis was higher in patients who received epinephrine injection and electrocoagulation (P = 0.041 and P = 0.039 respectively). Clinically, post-endoscopic sphincterotomy bleeding and further endoscopic hemostasis therapy increase the complication rate of pancreatitis and cholangitis. Realizing the effectiveness of each therapeutic modalities and appropriate management of different levels bleeding are important.