A systematic review and meta-analysis evaluated intracameral moxifloxacin given during cataract surgery for the prevention of postoperative endophthalmitis. Six randomized controlled trials with a total of 4,438 patients were included. Intracameral moxifloxacin significantly reduced the incidence of postoperative endophthalmitis compared with the control group (5 RCTs, hazard ratio 0.22; 95% CI 0.07ā0.77; p = 0.02). After excluding studies at high risk of bias, the protective effect remained statistically significant (3 RCTs, RR 0.183; 95% CI 0.038ā0.874; p = 0.03) with no evidence of heterogeneity (IĀ² = 0%, p = 0.65). There was no significant difference in postoperative changes in endothelial cell density (ECC) between moxifloxacin and control (3 RCTs, mean difference 22.17; 95% CI -8.53 to 52.88; p = 0.16). There was also no significant difference in central corneal thickness (CCT) (3 RCTs, mean difference -0.03; 95% CI -0.88 to 0.88). One study had a low risk of bias, three were of some concern and two were rated as having a high risk of bias. The systematic review was registered in the PROSPERO database (ID: CRD420251144067).