OBJECTIVE This systematic review assesses the effects of care bundles on the incidence of surgical site infections (SSIs). DATA SOURCES The search was conducted between February and May 2021, using PubMed, CINAHL, SCOPUS, Cochrane, and EMBASE databases. STUDY SELECTION Studies were included if they used systematic review methodology, were in English, used a quantitative design, and explored the use of care bundles for SSI prevention. A total of 35 studies met the inclusion criteria, and 26 provided data conducive to meta-analysis. DATA EXTRACTION Data were extracted using a predesigned extraction tool, and analysis was undertaken using RevMan (Cochrane, London, UK). Quality appraisal was undertaken using evidence-based librarianship. DATA SYNTHESIS The mean sample size was 7,982 (median, 840) participants. There was a statistically significant difference in SSI incidence in favor of using a care bundle (SSI incidence 4%, 703/17,549 in the care bundle group vs 7%, 1,157/17,162 in the usual care group). The odds ratio was 0.55 (95% confidence interval, 0.41-0.73; P <.00001), suggesting that there is a 45% reduction in the odds of SSI development for the care bundle group. The mean validity score for all studies was 84% (SD, 0.04%). CONCLUSIONS The results indicate that implementing care bundles reduced SSI incidence. However, because there was clinically important variation in the composition of and compliance with care bundles, additional research with standardized care bundles is needed to confirm this finding.