Purpose Endophthalmitis after intravitreal injection is a serious complication. There is limited data to support the use of post-injection antibiotics to prevent endophthalmitis. Current endophthalmitis rates after intravitreal injection in the literature are based on studies where patients routinely received post-injection antibiotics. This study retrospectively compares the rate of endophthalmitis in a cohort of patients receiving post-injection antibiotics to a group that does not. Methods A retrospective chart review was conducted comparing a 12 month period where patients received post-injection topical antibiotics for several days after intravitreal injection to the next 12 month period where no post-injection topical antibiotics were used. Cases of suspected endophthalmitis following intravitreal injection during this period were identified and reviewed. Results The rate of clinically suspected endophthalmitis in the cohort of patients receiving post injection antibiotics after intravitreal injection was 0.22%. The rate of clinically suspected endophthalmitis in the cohort of patients not receiving antibiotics was 0.20%. One culture positive case was found overall. The difference between the two groups is not statistically significant, p=0.75. Conclusion Rate of endophthalmitis after intravitreal injections administered in a clinical practice setting when aseptic technique is used is similar with or without the use of post-injection antibiotics.