OBJECTIVE Postoperative Propionibacterium endophthalmitis is a condition characterized by exacerbations and remissions that has often been accompanied by recurrence after treatment. The purpose of this study is to evaluate the efficacy of initial therapies in preventing recurrent endophthalmitis and to assess the safety of intraocular lens (IOL) exchange performed during treatment of active endophthalmitis. METHODS The records of 22 patients with culture-proven Propionibacterium endophthalmitis treated at one facility were retrospectively reviewed. RESULTS Two patients presented acutely, were treated with intraocular antibiotic injection alone, and experienced no recurrent inflammation. Twenty patients presented with chronic, delayed-onset pseudophakic endophthalmitis. Eight of these were treated initially with intraocular antibiotic injection alone, and recurrent endophthalmitis developed in seven. Twelve patients with chronic endophthalmitis were initially managed surgically with either pars plana vitrectomy or IOL exchange. Four of the 12 experienced recurrent endophthalmitis. Patients undergoing capsulectomy as part of initial management experienced the lowest rate of recurrent endophthalmitis. Eight patients eventually underwent total capsulectomy and IOL explantation, seven of whom had IOL exchange. None of these eight patients had recurrent endophthalmitis. In seven of the eight, persistent bacterial colonization of the lens capsular remnants was demonstrated. CONCLUSIONS These data suggest that recurrent Propionibacterium endophthalmitis is due to persistence of viable organisms sequestered within lens capsular remnants, and that initial therapy directed toward surgical removal of these sequestered organisms results in a reduced frequency of recurrent endophthalmitis. Intraocular lens exchange with complete capsular removal during active endophthalmitis was not associated with recurrent or persistent endophthalmitis.