Background: Endoscopic retrograde cholangiopancreatography, uses a combination of both endoscopy and fluoroscopy for diagnosis and treatment of hepatobiliary disorders. ERCP is generally considered to be safe and effective. Post-ERCP complication rates vary widely depending on the complexity of the intervention and the individual patient. Acute pancreatitis is the most common complication following ERCP maneuver, which is reported to occur in 2–10% of patients overall (varying between 2–4% in low risk patients up to 8–40% in high-risk patients). Aim: The study is designed to evaluate the clinical significance of 4-hour post endoscopic retrograde cholangiopancreatography amylase level as an early predictor of post ERCP pancreatitis. This will help to decide when to admit or discharge patient following ERCP, to early diagnose and treat post ERCP pancreatitis and hence spare major hospital resources. Patients and Methods: This study is a prospective cohort study, conducted in theendoscopy unit in Suez Canal university hospital, including adult patients of both sexes eligible for ERCP, excluding patients with pre ERCP pancreatitis, previous ERCP or patients with renal failure. Results: Thisstudy included 86 patients candidate for ERCP of whatever indication excluding patients with pre-endoscopic pancreatitis. In this study pancreatitis occurred in 14 patients out of 86(16.3%).4 hours serum amylase level was significantly higher in patients with post ERCP pancreatitis than in patients without post ERCP pancreatitis (P=0.001). 4hours post ERCP serum amylase is a significant predictor for early prediction of occurrence of PEP. Conclusions: Rising of serum amylase 4 hours post endoscopic retrograde cholangiopancreatographyabove 3.5 ULR is a significant predictor and patient with this level should be admitted and early treated