To evaluate the efficacy of vitrectomy with vancomycin for the treatment of experimental Bacillus cereus endophthalmitis. Endophthalmitis was initiated in rabbits via intravitreal injection of 100 colony-forming unit B. cereus. Treatment groups included 25-gauge transconjunctival sutureless vitrectomy with intravitreal vancomycin (1 mg) or vancomycin alone. Groups were treated at 4, 5, or 6 hours after infection. At 48 hours (for 4-hour and 5-hour groups) or 36 hours (for the 6-hour group) after infection, eyes were analyzed by electroretinography, histology, and inflammatory cell counts. Treatment with vitrectomy/vancomycin at 4 hours resulted in significantly greater retinal function compared with that of vancomycin alone. Intraocular inflammation after treatment at 4 hours was minimal for both the treatment groups. Treatment with vitrectomy/vancomycin or vancomycin alone at 5 hours or 6 hours after infection resulted in similar levels of retinal function loss (i.e., >90%) and significant intraocular inflammation. These results demonstrate that vitrectomy may be of therapeutic benefit in the treatment of B. cereus endophthalmitis but only during the early stages of infection.