BACKGROUND: Breast implant-associated infection and capsular contracture are challenging complications that can result in poor outcomes following implant-based breast surgery. Antimicrobial irrigation of the breast pocket or implant is a widely accepted strategy to prevent these complications, but the literature lacks an evidence-based consensus on the optimal irrigation solution. OBJECTIVES: The objective of this systematic review was to compare clinical outcomes, specifically capsular contracture, infection, and reoperation rates, associated with the use of antibiotic, antiseptic, and saline irrigation. METHODS: A systematic review was performed in March 2020 based on the following search terms: "breast implant," "irrigation," "antibiotic," "bacitracin," "antiseptic," "povidone iodine," "betadine," "low concentration chlorhexidine," and "hypochlorous acid." Capsular contracture, infection, and reoperation rates were compared by analysis of forest plots. RESULTS: Out of the 104 articles screened, 14 met the inclusion criteria. There was no significant difference in capsular contracture rates between antibiotic and povidone-iodine irrigation, although the data comparing these 2 groups were limited and confounded by the concurrent use of steroids. Antibiotic irrigation showed a significantly lower rate of capsular contracture compared with saline irrigation and a lower rate of capsular contracture and reoperation compared with no irrigation at all. Povidone-iodine was associated with lower rates of capsular contracture and reoperation compared with saline irrigation but there were no data on infection rates specific to povidone-iodine irrigation. CONCLUSIONS: Our study supports the use of antibiotics or povidone-iodine for breast implant irrigation. Further research is required to better determine which of these 2 irrigation types is superior.