We treated five patients for postoperative endophthalmitis who demonstrated an initially good response to intravitreal management of their infection and then suffered a later recurrence. Four of the five patients received a single intravitreal injection of antibiotics as the only intravitreal therapy, and the fifth patient received a single antibiotic injection in addition to a partial vitrectomy. All recurrent infections occurred between 10 and 21 days after the original intravitreal injection of antibiotics. At the time of the recurrence, all five patients remained culture positive with the same organism that was initially isolated. The bacterial species isolated were S. epidermidis, group D streptococcus, P. acnes, P. mirabilis, and P. aeruginosa. All patients were ultimately sterilized with repeated intravitreal injections of antibiotics, vitrectomy, and/or intraocular lens removal. Factors that were related to recurrent infection were marginal susceptibility of the organism to the originally injected antibiotics, infection with a slowly replicating organism, and infection with a gram-negative bacillus. A single intravitreal injection of antibiotics may only partially treat bacterial endophthalmitis. Patients should be observed for at least 3 weeks following treatment of endophthalmitis for recurrence of their infection, and aggressive management, including vitrectomy and repeated intravitreal injections of antibiotics, should be used to treat recurrent infections.