We report the first case of clinically diagnosed endogenous endophthalmitis caused by Histoplasma capsulatum var. capsulatum in a patient with the acquired immune deficiency syndrome.Interventional case report and literature review.Pars plana vitrectomy and scleral buckling procedure in the left eye with intravenous and intravitreal amphotericin in both eyes.The clinical features, culture results, visual outcome, and complications were studied.This case demonstrates a bilateral endophthalmitis with severe subretinal exudation, choroidal granulomas, and intraretinal hemorrhage leading to exudative bilateral retinal detachments. Vitreous cultures grew H. capsulatum var. capsulatum. Treatment consisted of intravenous amphotericin, intravitreal amphotericin (both eyes), pars plana vitrectomy (left eye), and scleral buckling procedure (left eye) with resulting counting fingers vision (right eye) and 20/300 (left eye). Four cases of Histoplasma endophthalmitis have been reported previously, all of which had a documented history of disseminated histoplasmosis and resulted in enucleation.H. capsulatum should be considered a possible etiologic agent of endophthalmitis, especially in patients with a history of disseminated histoplasmosis and/or immune deficiency.