Sixteen studies with patients undergoing shoulder surgery were included in this systematic review and network meta-analysis comparing the effectiveness of topical preparations used to reduce Cutibacterium acnes (C. acnes) infection. Topical preparations compared in this analysis include: benzoyl peroxide (BPO), BPO combined with clindamycin, chlorhexidine gluconate (CHG), hydrogen peroxide (H2O2), povidone-iodine, and water with soap. Pooled outcomes of interest included the reduction in the number of positive C. acnes cultures and adverse events related to the preparations. BPO significantly reduced the odds of a positive C. acnes culture compared to placebo or soap and water (OR 0.14 95% CI 0.05-0.36). No statistically significant differences were found for other preparations. The findings suggest BPO as the most effective topical agent for reducing C. acnes infections in shoulder surgery, though further studies are needed to determine the optimal pre-operative application regimen.