To characterize features and outcomes of intravenous drug use (IVDU)-associated endophthalmitis.Retrospective cross-sectional study.A retrospective chart review of all cases of endophthalmitis seen between September 2006 and November 2014 at a single academic referral center was performed. All cases of IVDU-associated endophthalmitis were identified and characterized.Ophthalmic examination findings, microbial results, visual outcomes, and secondary ocular sequelae.Thirty patients (32 eyes) with IVDU-associated endophthalmitis were identified, which represented 9% of all endophthalmitis patients (n = 338) and 44% of all endogenous endophthalmitis patients (n = 68). Mean follow-up was 11 months. All eyes had vitritis, 6 had hypopyon, and 2 had subretinal abscesses. Twenty eyes had macular involvement, 8 eyes had no macular involvement, and media opacities precluded macular assessment in 4 eyes. Initial treatment was needle vitreous biopsy with intravitreal antibiotics ("tap and inject") in 25 eyes (78%) and pars plana vitrectomy (PPV) in 6 eyes (19%); 1 patient refused ocular treatment. An organism was identified from at least 1 source in 75% of eyes (24/32): 59% fungal, 16% bacterial, 22% negative cultures, and 3% refused ocular cultures. Mean visual acuity improved significantly between initial examination and final follow-up (1.64 logMAR to 0.91 logMAR, P < 0.0001). At final follow-up, 90% of eyes had improved vision compared with presentation, 31% of eyes had 20/40 or better vision, and 25% of eyes had 20/200 or worse vision. Twenty-one eyes (66%) required PPV for their infection-6 initially and 15 secondarily after tap and inject. Sixty-nine percent of eyes (9/13) that had cultures sent from a secondary PPV had positive cultures, despite almost all receiving appropriate intravitreal antibiotic therapy at the time of the tap and inject. Eight patients (27%) had extraocular signs of infection. Twenty eyes (63%) suffered secondary ocular sequelae.This represents the largest series of IVDU-associated endophthalmitis. Bacterial etiologies constitute an important share of cases. A majority of patients eventually required PPV and there was frequent culture positivity even after tap and inject with appropriate antibiotics; therefore, early PPV may have an important role in management.