ABSTRACT: To identify the factors affecting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).We systematically searched databases for relevant studies published from inception to November 2013.A meta-analysis of 11 randomized trials (n = 2497) revealed a significant reduction in PEP in patients who received NSAIDs compared with that in patients who received placebo (relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85; P = 0.005). In subgroup analysis by treatment type, indomethacin had no significant effect (RR, 0.66; 95% CI, 0.38-1.15; P = 0.14), whereas other NSAIDs showed significant benefit (RR, 0.51; 95% CI, 0.29-0.91; P = 0.02). Only rectal administration significantly reduced the incidence of PEP (RR, 0.43; 95% CI, 0.32-0.58; P < 0.00001). The risk for PEP was the lowest among patients who received NSAIDs before ERCP (RR, 0.48; 95% CI, 0.29-0.78; P = 0.003). NSAIDs did not significantly reduce the risk of PEP in men (RR, 0.61; 95% CI, 0.34-1.09), patients with sphincter of Oddi dysfunction (RR, 0.98; 95% CI, 0.38-2.54), or patients with pancreatic duct injection (RR, 0.64; 95% CI, 0.35-1.18).Rectal administration of NSAIDs (especially diclofenac), before ERCP, seemed to be the most effective strategy for preventing PEP.