AIM: To compare the hemostatic efficacy between epinephrine injection alone and epinephrine injection combined with thermotherapy for delayed postendoscopic sphincterotomy (ES) bleeding. METHODS: Cases with delayed post-ES bleeding undergoing epinephrine injection alone (epinephrine injection group, n = 26) or epinephrine combined with thermotherapy (combination therapy group, n = 33) in our institution between 1999 and 2007 were retrospectively investigated. The main outcome measurements were: initial endoscopic hemostasis, rebleeding, complications, requirement of angiographic embolization or surgery, requirement for blood transfusion, and mortality. RESULTS: The initial hemostatic efficacy was 96.2% for epinephrine injection alone and 100% for combination therapy ( P = 0.44). There were four patients with re-bleeding in each group (16.0% vs 12.1%, P = 0.72). There was only one complication of pancreatitis from the combination therapy group. Three patients (11.5%) in the epinephrine injection group and one patient (3%) in the combination therapy group required angiographic embolization or surgery ( P = 0.31). The total number of blood transfusions was not significantly different between the two groups (3.5 ± 4.6 U vs 3.5 ± 4.5 U, P = 0.94). There was no bleeding-related death in either group. CONCLUSION: Epinephrine injection alone is as effective as epinephrine injection combined with thermotherapy for the management of delayed post- ES bleeding.