To evaluate the efficacy and safety of diclofenac compared with placebo for the prevention of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis.

We conducted a comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane from their inception to November 2025, focusing on randomized controlled trials (RCTs) evaluating diclofenac versus placebo in the prevention of post-ERCP pancreatitis. Meta-analyses were performed using a random-effects model. Odds ratios (ORs), hazard ratios (HRs), and mean differences (MDs) were calculated with 95% confidence intervals (CIs) to assess the efficacy and safety of diclofenac versus placebo. 

Four randomized trials assessing low-dose diclofenac for prevention of post-ERCP pancreatitis (PEP) were included (n=708; diclofenac n=353, control n=355). Overall, diclofenac did not significantly reduce the incidence of PEP compared with control (pooled RR = 0.55; 95% CI, 0.20–1.50; p = 0.24). However, there was marked variability across studies (I² = 70.7%, p = 0.02). Trials evaluating rectal diclofenac demonstrated substantial benefit, particularly Khoshbaten 2008 (RR = 0.15; 95% CI, 0.04–0.65) and Otsuka 2012 (RR = 0.21; 95% CI, 0.05–0.90). In contrast, studies using low-dose rectal diclofenac (Katoh 2020) or oral administration (Cheon 2007) showed no protective effect. These findings suggest that clinical efficacy depends on dose and route of administration, with higher-dose rectal diclofenac showing the greatest preventive effect.

Rectal diclofenac is a safe and effective prophylaxis for post-ERCP pancreatitis, showing greater benefit than placebo, especially at higher doses. Its efficacy is route-dependent, as oral and low-dose formulations do not provide meaningful protection. Overall, rectal administration offers the most reliable preventive effect without increasing adverse events.