<b><i>Purpose:</i></b> The main objective of this study was to investigate the microbiological spectrum of endophthalmitis after anti-VEGF injections and to compare streptococcal with non-streptococcus-associated cases with regard to baseline characteristics and injection procedure. <b><i>Methods:</i></b> Retrospective, international multicenter study of patients with culture-positive endophthalmitis after intravitreal anti-VEGF injection at 17 different retina referral centers. <b><i>Results:</i></b> Eighty-three cases with 87 identified pathogens were included. Coagulase-negative staphylococci (59%) and viridans streptococci (15%) were the most frequent pathogens found. The use of postoperative antibiotics and performance of injections in an operating room setting significantly reduced the rate of streptococcus-induced endophthalmitis cases (<i>p</i> = 0.01 for both). <b><i>Conclusion:</i></b> We found a statistically significant lower rate of postinjectional local antibiotic therapy and operating room-based procedures among the streptococcus-induced cases compared to cases caused by other organisms.