BACKGROUND: Cutibacterium acnes is a common pathogen associated with surgical site infection after shoulder surgery; current standard of care products are largely ineffective at reducing C acnes bacterial burden before surgery. The purpose of this systematic meta-analysis was to assess the efficacy of peroxide-containing solutions (PCS) in decreasing the C acnes burden on the shoulder. METHODS: This was a systematic review of all level I and II studies investigating the effect of peroxidase-containing products for skin preparation. We extracted data regarding demographics, treatment details and timing, study methodology, and culture positivity. Forest plots were used to determine the pooled efficacy of peroxide solutions versus control. RESULTS: Seven studies with 412 patients were eligible for inclusion. Notable heterogeneity was observed in the manner and timing of peroxide application. Two studies applied PCS at the time of surgery; four studies applied PCS in the 24- to 72-hour period leading up to culture acquisition. Compared with the placebo, peroxide significantly diminished C acnes culture positivity (Hazard Ratio 0.174, P = 0.009). When considering using peroxide-containing products in the period leading up to surgery or at the time of surgery, in addition to standard preparation, the addition of peroxide significantly diminished C acnes culture positivity (HR 0.467, P = 0.004). Owing to study heterogeneity, we could not make notable comparisons based on the timing or duration of benzoyl peroxides application. CONCLUSIONS: Despite heterogeneity in study design, pooled results of high-quality data suggest that the addition of PCS can markedly reduce C acnes bioburden. This review was not able to identify the ideal regimen for the utilization of PCS for reduction of C acnes burden. LEVEL OF EVIDENCE: Level II.