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There is continuing debate regarding the safety, efficacy, and necessity of intracameral antibiotics to prevent postoperative endophthalmitis. We summarize the most recent evidence-based publications that either support or caution against this practice.Several additional large, international retrospective clinical studies found a significant reduction in endophthalmitis rates with intracameral antibiotic prophylaxis. Many surgeons are looking for alternatives to vancomycin for intracameral prophylaxis because of its association with the rare but sight-threatening complication of hemorrhagic occlusive retinal vasculitis. Although most efficacy data has been reported for intracameral cefuroxime, one of the largest clinical studies to date shows convincing efficacy with intracameral moxifloxacin prophylaxis. This same study reported a significant benefit with intracameral moxifloxacin following posterior capsular rupture, and surgeons should consider intracameral prophylaxis in these high risk cases.Despite mounting evidence that routine prophylaxis with intracameral cefuroxime and moxifloxacin reduce the endophthalmitis rate following cataract surgery, many surgeons have not adopted this practice. Reasons include lack of level 1 evidence from randomized trials, and the potential risks from compounding or mixing antibiotic solutions when no approved formulations are commercially available. Countries with commercially approved intraocular antibiotic formulations have the highest adoption rates of routine intracameral prophylaxis.