ObjectiveTo analyze the incidence of infectious endophthalmitis after intravitreal injection of three anti-vascular endothelial growth factor (VEGF) drugs. MethodsA single-center retrospective study. From January 1, 2020 to June 30, 2025, a total of 7 534 patients who received intravitreal anti-VEGF injections at Department of Pharmacy of Zhengzhou Second Hospital were included in the study. The administered drugs included ranibizumab, aflibercept, and conbercept. By reviewing the hospital information system to determine whether patients developed endophthalmitis after injection and collecting clinical data, the Charlson Comorbidity Index (CCI) was calculated. Among the 7 534 cases, there were 4 008 males and 3 526 females, with a mean age of (60.22±13.33) years. The diagnoses included neovascular age-related macular degeneration (1 980 cases), diabetic macular edema (2 974 cases), retinal vein occlusion (1 866 cases), choroidal neovascularization (556 cases), and neovascular glaucoma (158 cases). Intravitreal injections comprised ranibizumab (2 813 cases), aflibercept (1 716 cases), and conbercept (3 005 cases), which served as the basis for grouping. A total of 17 109 anti-VEGF injections were administered, including 6 230 ranibizumab, 4 213 aflibercept, and 6 666 conbercept injections, with a median injections of 2 (1, 3) per eye. Intergroup comparisons were performed using the χ2 test, and Cox proportional hazards regression models were employed to analyze risk factors for infectious endophthalmitis. ResultsAmong 7 534 cases, 7 cases (0.092%, 7/7 534) developed endophthalmitis after intravitreal injection of anti-VEGF drugs, including 1 case (0.04%, 1/2 813) in the ranibizumab group, 2 cases (0.12%, 2/1 716) in the aflibercept group, and 4 cases (0.13%, 4/3 005) in the conbercept group. The incidence of endophthalmitis in the conbercept group was higher than that in the ranibizumab and aflibercept groups, but the difference was not statistically significant (P=0.494). Univariate Cox analysis showed that age, gender, fundus diseases, CCI, diabetes comorbidity, and anti-VEGF drugs were not correlated with the occurrence of endophthalmitis (P＞0.05). The median time to endophthalmitis onset after injection was 4 days in the 7 cases. Intravitreal injections of vancomycin and ceftazidime were administered. ConclusionsThe incidence of infectious endophthalmitis following intravitreal anti-VEGF injections was 0.092%, with no significant difference observed among the three drugs. No correlation was found with age, fundus disease, or number of injections.