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Objective: To compare the diclofenac sodium intramuscular prophylaxis given with standard treatment in patients having ERCP was compared with standard treatment alone with respect to frequency and severity of pancreatitis within 48 hours after the procedure. Study Design: Randomized Controlled Trial. Setting: Department of Gastroenterology, Hepatology, and GI Endoscopy, SZABMU, Pakistan Institute of Medical Sciences, Islamabad. Period: August 2021 and April 2022. Material & Methods: The study enrolled 160 patients with obstructive jaundice with or without pruritus (20-70 years). Each group consisted of 80 patients. A prophylactic dose of 75 mg of diclofenac sodium was administered intramuscularly to Group A in addition to standard treatment, while standard treatment was given to Group B alone. The standard treatment for PEP was antibiotics (Cefoperazone/Sulbactam 2g IV) for both groups. IV dormicum (midazolam) was given to both groups as sedation. All patients were tested for lipase and amylase after the procedure to detect any complications. They were also monitored for abdominal pain at 4 and 24 hours after the procedure. Results: In patients of Group A (n=80), the mean age was 47.1 years ± 8.4 SD, whereas in patients in Group B (n=80), the mean age was 47.5 years ± 7.4 SD. In Group A, 3.8% of patients (n=3/80) developed PEP, while 11% (n=11/80) developed PEP (p=0.025). Intramuscular diclofenac sodium was more efficient at preventing PEP when compared to the control group on standard treatment alone, on all of the following parameters: (1) the proportion of patients that did not develop PEP, (2) the rate of patients that developed PEP, and (3) the average quantity of days that patients were sick. In both groups A and B, the PEP diagnosis was mild and the patients were discharged within 2-3 days of diagnosis. PEP efficacy was not significantly different across age groups or genders in both treatment groups (p>0.05). Conclusion: Diclofenac sodium is significantly more effective than standard treatment alone for intramuscular pancreatitis prophylaxis after ERCP. [ABSTRACT FROM AUTHOR]