In 1987, the authors reported the successful eradication of infection in 16 patients with culture-proven acute exogenous bacterial endophthalmitis using intravitreal but no systemic antibiotics. They retrospectively reviewed additional consecutive cases since then to determine if the initial omission of systemic antibiotics remained reasonable. Twenty patients had culture-proven endophthalmitis. Four patients initially received systemic antibiotics for orbital cellulitis (2 patients), prevention of a possible scleral buckle infection (1 patient), and ascending cholangitis (1 patient). The remaining 16 patients were treated initially with intravitreal antibiotics only. Three of these additional 16 patients ultimately required systemic antibiotics for orbital cellulitis (1 patient), infectious scleritis (1 patient), and prevention of central nervous system infection with Neisseria meningitidis (1 patient). Only in one patient who had a neglected endophthalmitis and in whom an orbital cellulitis ultimately developed were we unable to clear the intraocular infection. In the overall series of 32 patients, cultures yielded staphylococcal species in 16 eyes, gram-positive bacilli in 3, streptococcal infection in 5, gram-negative cocci in 1, and gram-negative bacilli in 7. Half of the 14 specimens (1 aqueous and 13 vitreal) collected at the time of 16 reinjections in 13 eyes yielded organisms. Half (16/32) of the eyes attained visual acuity of 20/40 or better; 87.5% (28/32) attained visual acuity of 20/400 or better. Therapy with intravitreal antibiotics without systemic antibiotics is reasonable, unless the infection has extended (or is at risk to extend) beyond the globe. Such evidence includes an elevated temperature or leukocyte count, corneal ring abscess, proptosis, loss of extraocular movements, scleral abscesses or infectious scleritis, and, perhaps, the presence of a scleral buckle.