Efficacy of prophylactic indomethacin for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in general patients remains controversial. To address this, we conducted a meta-analysis of clinical trials specifically on rectal indomethacin in prevention of PEP in consecutive patients undergoing ERCP. We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases to identify randomized, double-blind, controlled clinical trials on rectal indomethacin in the prevention of PEP in consecutive patients undergoing ERCP. Primary outcome was the overall rate of PEP. Secondary outcomes were the overall rates of moderate to severe PEP and mild PEP. Six studies, with a total of 2473 patients, were included. Overall rate of PEP was 7% (95% CI, 6-9%). No statistical difference was observed in overall rates of PEP (OR, 0.67; 95% CI, 0.46-1.00, P = 0.050) and, additionally, rates of moderate to severe (OR, 0.66; 95% CI, 0.28-1.56, P = 0.345) or mild (OR, 0.71; 95% CI, 0.45-1.10, P = 0.127) PEP between indomethacin and placebo. In a contemporary meta-analysis of available randomized controlled trials of consecutive patients undergoing ERCP, rectal indomethacin did not show significant prevention effect of post-ERCP pancreatitis.