BackgroundCutibacterium acnes (C. acnes), a common pathogen, contributes significantly to infections in shoulder surgery. Prevention of shoulder infection is crucial to improve postoperative functional recovery and reduce costs. This study aimed to perform a systematic review and meta-analysis to assess the safety and efficacy of 5% benzoyl peroxide (BPO) application in the shoulder to decrease C. acnes.MethodsThree electronic databases were searched as follows: PubMed, Embase, and the Cochrane Library databases. Data extraction for this study was performed by two independent reviewers, and only level I and level II studies were included. The outcome data sources of individual studies were pooled. The fixed-effect model was used to determine the meta-analysis.ResultsThere were five level I studies and five level II studies. The results showed that the 5% BPO group had a lower risk of C. acnes positivity [OR, 0.21 (0.15, 0.30), I-2 = 24, p < 0.00001]. The pooled analysis results showed that there was no significant difference in the ability of 5% BPO and 5% BPO + clindamycin to reduce C. acnes. However, the lower rate of adverse events was significantly in favour of the non-BPO group compared with the 5% BPO group.ConclusionBPO can decrease C. acnes in the shoulder to prevent infection. However, the combination of BPO and clindamycin does not enhance this effect further.