OBJECTIVES: To systematically assess the impact of sodium glucose co-transporter-2 inhibitors (SGLT2) inhibitors treatment on urinary tract infections (UTIs) and genital infections in patients with type 2 diabetes. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with placebo or active antidiabetic drugs with a duration of 12 weeks or longer, among patients with type 2 diabetes. Paired reviewers independently screened citations, assessed risk of bias, and extracted data. We pooled effect estimates using Mantel-Haenszel relative risk with 95% confidence intervals, and used the GRADE method to rate the quality of evidence. RESULTS: In total, 77 RCTs involving 50,820 participants were included. The pooled analyses showed no significant difference in urinary tract infections (UTIs) between SGLT2 inhibitors versus control (2,526/29,086 vs. 1,278/14,940; risk ratio (RR) 1.06, 95% confidence interval (CI) 0.99 to 1.13, low quality evidence), but suggested increased risk of genital infections with SGLT2 inhibitors (1,521/24,017 vs. 216/12,552; RR 3.83, 95% CI 3.34 to 4.40, RD 521 more, 95% CI 431 more to 626 more per 1000 over 5 years; high quality evidence). Dapagliflozin - an individual drug of SGLT2 inhibitors - showed increased risks of UTIs (RR 1.34, 95% CI 1.11 to 1.62) and genital infections (RR 3.80, 95% CI 2.57 to 5.62), as well as events suggestive of UTIs (RR 1.33, 95% CI 1.10 to 1.61; high quality evidence) and of genital infections (RR 4.50, 95% CI 3.24 to 6.25; high quality evidence). CONCLUSIONS: The impact of SGLT2 inhibitors on the risk of UTIs remains uncertain, high quality evidence shows a clinically important increase in the risk of genital infections in type 2 diabetes patients using this drug class.