Purpose To report the incidence of endophthalmitis following intravitreal injection using a standardized injection procedure. Design Two randomized clinical trials. Methods Nonpreserved intravitreal triamcinolone acetonide in prefilled syringes (Allergan, Inc, Irvine, California, USA) was injected intravitreally in the Diabetic Retinopathy Clinical Research Network (DRCR net) and the Standard Care vs COrticosteroid for REtinal Vein Occlusion (SCORE) clinical trials. The standardized injection procedure did not include the use of topical antibiotics during the days prior to the injection. Results As of December 31, 2006, 1,378 intravitreal injections (538 eyes) have been administered in the Diabetic Retinopathy Clinical Research Network Diabetic Macular Edema trial and 631 injections (301 eyes) in Standard Care vs COrticosteroid for REtinal Vein Occlusion. There was one case of endophthalmitis in the 2,009 injections to date (0.05%, 95% confidence interval 0.001% to 0.277%). Conclusion A low rate of endophthalmitis is achievable using a standardized procedure for intravitreal injection without prescribing antibiotic prophylaxis on the days prior to the injection.