Background: Endoscopic Retrograde Cholangiopancreatography (ERCP) has evolved into a therapeutic procedure, with endoscopic sphincterotomy (ES) being the most common intervention. Effective hemostatic techniques involve balloon tamponade, coagulation, and hemoclips for post-sphincterotomy bleeding (PSB). This study aimed to evaluate the efficacy and safety of balloon tamponade in controlling post-sphincterotomy bleeding during ERCP. Methods: This prospective and retrospective cohort study included 18 eligible patients diagnosed with post sphincterotomy bleeding during ERCP categorized into 2 groups: group 1 (G1, n=14) successful hemostasis and G2 (n=4) non-successful hemostasis. Assessments comprised history, physical examination, laboratory tests (complete blood count, international normalized ratio, liver and kidney function, blood glucose, serum electrolytes, magnetic resonance cholangiopancreatography (MRCP), and ERCP). Results: Statistically significant differences were revealed between the two groups as regards hemostasis after 3 minutes of tamponading, extended hemostasis to 5 minutes, and adrenaline injection; among group 1 (71.4%) of patients had successful hemostasis at 3 minutes, while none of the patients among group 2 (0%) had successful hemostasis(P=0.02). Also, (28.6%) of patients inGroup1 had successful hemostasis at 5 minutes, while none of the patients inGroup2 (0%) had successful hemostasis(P=0.005). As regards adrenaline injection, (50%) of patients in group 2 had successful adrenaline injections, while all the patients (100%) among group 1 had no adrenaline injection(P=0.005). Conclusion: A complete understanding of managing bleeding of various severities, as well as potential adverse events, is highly important in delivering efficient patient therapies. Therefore, balloon tamponade could be more effective safer in management of post sphincterotomy bleeding during endoscopic retrograde cholangiopancreatography.