Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure combining endoscopy and fluoroscopy to diagnose and treat pancreaticobiliary disorders such as bile duct stones, strictures, and cholangitis. Despite its therapeutic value, ERCP carries a relatively high complication risk of about 10%, with severe complications occurring in roughly 24% of those affected and mortality rates between 0.2% and 0.7%. The most common and significant complication is post-ERCP pancreatitis (PEP), occurring in 2% to 10% of average patients and up to 40% or higher in high-risk groups. PEP ranges from mild, self-limiting inflammation to severe, life-threatening conditions including pancreatic necrosis and multi-organ failure. PEP arises from mechanical trauma, hydrostatic injury, chemical irritation, or infection during ERCP that activates inflammatory pathways within the pancreas. Key patient-related risk factors include young age, female sex, prior pancreatitis, and sphincter of Oddi dysfunction; procedural factors include difficult biliary cannulation, pancreatic duct manipulation, and precut sphincterotomy. Preventive strategies focus on minimizing mechanical injury and pharmacologic prophylaxis. Rectal NSAIDs (indomethacin, diclofenac) administered immediately before ERCP are well-supported for reducing PEP risk. Periprocedural aggressive intravenous hydration and prophylactic pancreatic duct stenting in high-risk cases also lower PEP incidence. Nitroglycerin, a smooth muscle relaxant acting via nitric oxide-mediated sphincter relaxation, has shown promise in PEP prevention, especially in patients contraindicated for NSAIDs. Clinical trials indicate that transdermal or sublingual nitroglycerin reduces PEP rates, and combined use with NSAIDs may enhance protection. However, current guidelines do not routinely recommend nitroglycerin due to limited consensus on its efficacy. Topical nitroglycerin, known to relax smooth muscles locally and used in anorectal conditions, might reduce sphincter of Oddi pressure without systemic side effects. This suggests potential benefit in lowering PEP incidence or severity when applied topically during ERCP, pending further investigation. This study aimed to investigate whether topical delivery of nitroglycerin can reduce the incidence rate of PEP or the severity of pancreatitis.