Endogenous Aspergillus flavus endophthalmitis with layering of inflammatory cells in the subretinal space and vitreous infiltration developed in a 35-year-old female intravenous drug abuser. The patient underwent a diagnostic and therapeutic vitrectomy within 48 hours of presentation, receiving intravitreal amphotericin B. Intravenous amphotericin also was administered several days later. Despite extensive retinal and vitreous involvement, the patient recovered useful vision because of the aggressive diagnostic and therapeutic approach.