IMPORTANCE: The conclusions from the multiple randomized clinical trials exploring the relationship between development of intussusception and rotavirus vaccination among neonates and infants have been controversial. OBJECTIVE: To evaluate the association between rotavirus vaccination and risk of intussusception. DATA SOURCES: For this systematic review and meta-analysis, PubMed, Web of Science, Cochrane library, and Embase databases were searched from January 1, 1999, through December 31, 2018, using no language restrictions. The search terms were rotavirus or RV (rotavirus vaccine) or HRV (human rotavirus vaccine), vaccin*, and intussusception. STUDY SELECTION: Randomized clinical trials of neonates and infants that compared the risk of intussusception after the vaccination with a placebo group were included. DATA EXTRACTION AND SYNTHESIS: A fixed-effects model was used to pool the data. Statistical heterogeneity was assessed with Q test and I2 statistic; relative risk (RR), risk difference (RD), and 95% CIs were calculated using the Mantel-Haenszel method. MAIN OUTCOMES AND MEASURES: The main outcome was the diagnosis of intussusception in the analysis. The pooled and subtotal results of RR, RD, and 95% CI for the risk of intussusception were estimated at 31 days, 1 year, and 2 years after vaccination. RESULTS: A total of 25 randomized clinical trials including 200鈥?94 participants (104鈥?47 receiving vaccine and 95鈥?47 receiving placebo) in 33 countries from 4 continents were included in this meta-analysis. Twenty cases of definite intussusception were diagnosed within 31 days after rotavirus vaccination, with 11 cases (55%) in the vaccine group and 9 cases (45%) in the placebo group (RD, 0.17 per 10鈥?00 infants [95% CI, -1.16 to 1.50 per 10鈥?00 infants], P = .80; RR, 1.14 [95% CI, 0.49 to 2.64], P = .77). Seventy-four cases were reported within 1 year, with 37 cases (50%) in the vaccine group and 37 cases (50%) in the placebo group (RD, -0.65 per 10鈥?00 infants [95% CI, -2.68 to 1.39 per 10鈥?00 infants], P = .53; RR, 0.84 [95% CI, 0.53 to 1.32], P = .45). Fifty-nine cases were reported within 2 years, with 29 cases (49%) in the vaccine group and 30 cases (51%) in the placebo group (RD, -0.48 per 10鈥?00 infants [95% CI, -3.64 to 2.69 per 10鈥?00 infants], P = .77; RR, 0.91 [95% CI, 0.55 to 1.52], P = .73). CONCLUSIONS AND RELEVANCE: Results of this systematic review and meta-analysis suggest that monovalent, pentavalent, monovalent human-bovine, oral bovine pentavalent, and human neonatal rotavirus vaccination was not associated with an elevated risk of intussusception among neonates or infants.