BACKGROUND: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). The beneficial effects of pharmacologic treatment of acute pancreatitis are unclear. Although the prophylactic use of NSAIDs for the reduction of the risk for pancreatic injury after ERCP has been assessed, the beneficial effects of NSAIDs on pancreatic injury are still being debated. OBJECTIVE: The aim of this study was to determine the effectiveness and tolerability of NSAIDs in the prophylaxis of post-ERCP pancreatitis (PEP). METHODS: MEDLINE (January 1966-January 2009), EMBASE (January 1966-January 2009), and the Cochrane Central Register of Controlled Trials (Issue 1, 2009) were searched using the key terms: pancreatitis, post-ERCP pancreatitis, nonsteroidal anti-inflammatory drugs, indomethacin, and diclofenac. The methods recommended by the Cochrane Collaboration and the Quality of Reporting Meta-Analyses guideline were used to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of NSAIDs in the prevention of PEP. RESULTS: Four multinational RCTs were included in the meta-analysis (969 patients). The pooled odds ratio for NSAIDs for mild PEP was 0.69 (95% CI 0.40-1.17; P = NS); moderate to severe PEP, 0.22 (95% CI, 0.05-1-01; P = 0.05); PEP (pooled), 0.44 (95% CI, 0.21-0-93; P = 0.03); in high-risk patients, 0.49 (95% CI, 0.17-1.39; P = NS); and in low-risk patients, 0.29 (95% CI, 0.12-0.71; P = 0.006). No evidence of publication bias was found. CONCLUSION: Based on the findings from the present systematic review of 4 RCTs, NSAIDs were effective and well tolerated in the prevention of PEP, especially in low-risk patients. (Curr Ther Res Clin Exp. 2009;70:323-334) (C) 2009 Excerpta Medica Inc.