To compare the incidence of endophthalmitis following intravitreal injection (IVI) with versus without topical antibiotic prophylaxis.We systematically searched PubMed, Embase, and the Cochrane Library from each database's inception through August 2024. The primary outcome measure was the endophthalmitis rates after IVI, while the secondary outcomes included the distribution and quantity of microorganisms and best-corrected visual acuity (BCVA) changes. Study quality was assessed using the Newcastle-Ottawa Scale. For the meta-analysis, pooled summary estimates were calculated using a random-effects model.Eighteen studies (3,138,778 IVIs; 1,426 endophthalmitis cases) showed no significant difference in endophthalmitis incidence between prophylaxis and no-prophylaxis groups (Odds Ratio (OR) 1.85, 95% credible interval (CI) 0.72-4.76; P=0.2). For microbial analysis, we selected eleven studies that demonstrated no significant difference in culture-positive rates between prophylaxis and non-prophylaxis groups (OR, 1.23; 95%CI, [0.53, 2.84]; p = 0.63). Four studies provided best-corrected visual acuity (BCVA) changes from baseline to final follow-up, antibiotic prophylaxis group showed a decrease by 4.5 ETDRS letters compared to the no-prophylaxis group, although this difference was not statistically significant (p=0.65).Topical antibiotics did not reduce endophthalmitis risk or improve visual outcomes post-IVI. Given potential risks, routine prophylaxis is not recommended.