The prophylactic use of antibiotics in endoscopic retrograde cholangiopancreatography (ERCP) is still controversial. To assess whether antibiotic prophylaxis reduces the rates of complications in patients undergoing elective ERCP. This systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. A comprehensive search of multiple electronic databases was performed. Only randomized controlled trials were included. The outcomes analyzed included bacteremia, cholangitis, sepsis, pancreatitis, and mortality. The risk of bias was assessed by the Cochrane revised Risk-of-Bias tool for randomized controlled trials. The quality of evidence was assessed by the Grading of Recommendation Assessment, Development, and Evaluation. Meta-analysis was performed using the Review Manager 5.4 software. Ten randomized controlled trials with a total of 1757 patients that compared the use of antibiotic and non-antibiotic prophylaxis in patients undergoing elective ERCP were included. There was no significant difference between groups regarding incidence of cholangitis after ERCP [risk difference (RD) = -0.02, 95% confidence interval (CI): -0.05, 0.02, P = 0.32], cholangitis in patients with suspected biliary obstruction (RD = 0.02, 95%CI: -0.08 to 0.13, P = 0.66), cholangitis on intravenous antibiotic prophylaxis (RD = -0.02, 95%CI: -0.05 to 0.01, P = 0.25), septicemia (RD = -0.02, 95%CI: -0.06 to 0.01, P = 0.25), pancreatitis (RD = -0.02, 95%CI: -0.06 to 0.01, P = 0.19), and all-cause mortality (RD = 0.00, 95%CI: -0.01 to 0.01, P = 0.71]. However, the antibiotic prophylaxis group presented a 7% risk reduction in the incidence of bacteremia (RD= -0.07, 95%CI: -0.14 to -0.01, P = 0.03). The prophylactic use of antibiotics in patients undergoing elective ERCP reduces the risk of bacteremia but does not appear to have an impact on the rates of cholangitis, septicemia, pancreatitis, and mortality.