To report the rates of endophthalmitis and the spectrum of causative organisms after intravitreal injection of anti-vascular endothelial growth factor agents and possible prevention strategies. Meta-analysis of the U.S. literature from 2005 to 2009 reporting endophthalmitis bacterial isolates after intravitreal injection of anti-vascular endothelial growth factor agents and comparison with reports of endophthalmitis bacterial isolates after intraocular surgery in the United States. Endophthalmitis after intravitreal injection occurred in 52 of 105,536 injections (0.049%) (95% confidence interval [CI], 0.038-0.065%). Among 50 cases of endophthalmitis with bacterial culture isolates, 24 (48.0% [95% CI, 34.8-61.5%]) were culture negative and 26 (52% [95% CI, 38.5-65.2%]) were culture positive. Among the 26 culture-positive isolates, causative organisms were coagulase-negative Staphylococcus in 17 cases (65.4% [95% CI, 46.0-80.6%]), Streptococcus species in 8 cases (30.8% [95% CI, 16.5-50.2%]), and Bacillus cereus in 1 case (3.8% [95% CI, 0.9-19.0%]). Streptococcus species were significantly more frequent after intravitreal injection than after intraocular surgery in the Endophthalmitis Vitrectomy Study (29 of 226 isolates, 9.0% [95% CI, 6.3-12.6%], P = 0.005), a report on clear corneal cataract surgery endophthalmitis (6 of 73 isolates, 8.2% [95% CI, 3.9-16.8%], P = 0.022), and a report on postvitrectomy endophthalmitis with no cases of Streptococcus species. Streptococcal isolates are approximately three times more frequent after intravitreal anti-vascular endothelial growth factor injection than after intraocular surgery. Strategies to consider minimizing oropharyngeal droplet transmission may include avoiding talking, coughing, and sneezing or wearing surgical masks.