PURPOSE: To present the results of a retrospective study regarding the clinical and economic impact of intracameral cefuroxime administration to prevent endophthalmitis during cataract surgery in a referral hospital. METHODS: This study included 16,902 eyes from patients who had undergone cataract surgery between 2013 and 2017. From May 2014 onwards, all patients received routine intracameral injections of 1 mg cefuroxime (10 mg/1 mL) after phacoemulsification. The prophylactic efficacy was evaluated using the relative risk ratio, whereas the economic impact was evaluated using number needed to treat to avoid endophthalmitis. RESULTS: Before introducing cefuroxime, 3,407 cataract surgeries were performed using the phacoemulsification technique, and 7 post-operatory cases of endophthalmitis occurred (0.2% incidence). After introducing the cefuroxime protocol, 13,495 surgeries were performed, and 4 endophthalmitis cases were registered (0.03% incidence). Cefuroxime was identified as a protective factor against the development of endophthalmitis [risk ratio = 14%, p=0.002, 95% confidence interval (CI) 95%, 4%-49%], with an economic impact of number needed to treat = 568. The potential savings with cefuroxime was approximately US $2,334.36 for every 568 patients treated. CONCLUSION: The incidence of endophthalmitis decreased by 86% (risk ratio = 14%, p=0.002, 95% CI, 4%-49%) after introducing intracameral cefuroxime prophylaxis at the study hospital. The results presented herein provide strong evidence for the use of cefuroxime in endophthalmitis prophylaxis after phacoemulsification surgeries, outperforming the alter-native by providing both economic and clinical benefits.