OBJECTIVE To determine the rate of endophthalmitis and assess risk factors for development of endophthalmitis following open globe injury (OGI). METHODS A retrospective chart review of all patients treated for OGI at the University of Michigan from January 2000 to July 2017 was conducted. Exclusion criteria included intravitreal injection or intraocular surgery in the 30 days prior to injury or less than 30 days of follow-up. A total of 586 out of 993 open globe injuries were included in the study. The main outcome measure was the rate of endophthalmitis. RESULTS In this study, 25/586 eyes (4.3%) had endophthalmitis. Of these, 12/25 eyes (48.0%) presented with endophthalmitis and 13/25 eyes (52.0%) developed endophthalmitis after globe closure. Multivariate analysis identified time to globe repair (OR 4.5, CI 1.9-10.7, p = 0.0008), zone I injury (OR 3.6, CI 1.1-11.0, p = 0.0282), and need for additional surgery (OR 5.5, CI 1.5-19.7, p = 0.0092) as factors associated with increased risk of developing endophthalmitis. Subconjunctival antibiotic injection at the time of globe closure (OR 0.3, CI 0.1-0.7, p = 0.0036) was associated with decreased risk of developing endophthalmitis. CONCLUSIONS Prompt globe closure and subconjunctival antibiotics may reduce the risk of endophthalmitis in OGI. Furthermore, our practice of a one-time dose of systemic prophylactic antibiotics, and intravitreal antibiotics if intraocular foreign body (IOFB) removal is delayed, was not found to increase the rate of endophthalmitis.