PURPOSE: To describe the clinical presentation, management, and visual outcomes of 6 eyes with endophthalmitis after Descemet stripping endothelial keratoplasty (DSEK). DESIGN: Retrospective case series. METHODS: Setting: Tertiary, academic eye center. StudyPopulation: Individuals developing endophthalmitis after DSEK at the Duke Eye Center from January 1, 2009, to January 1, 2018, with at least 6 months of follow-up. ObservationProcedure: Retrospective chart review. OutcomeMeasures: Diagnostic procedures, microbiological yield, and visual outcomes. RESULTS: Six eyes of 6 patients were identified. Mean time from surgery to presentation was 51 days (range, 4-137 days). Dense vitreous opacities were present in all cases. Five of 6 cases (83%) had culture-proven infectious endophthalmitis (2 Candida glabrata, 2 coagulase-negative Staphylococcus, 1 Streptococcus pneumoniae). Aqueous tap yielded positive culture in 2 of 2 cases with adequate sample (100%); needle vitreous tap yielded positive culture in 0 of 3 cases. One eye underwent vitrectomy on presentation, and 3 eyes (50%) underwent subsequent vitrectomy for persistent endophthalmitis after a mean of 37 days. Mean pre-endophthalmitis visual acuity (VA) was 20/64; mean VA at 6 months was 20/2069 (average 15 ETDRS lines lost). VA at 6 months was light perception or no light perception in 3 of 6 cases (50%). One eye underwent enucleation at 6 months, and 1 eye became phthisical 1 year after endophthalmitis. CONCLUSIONS: DSEK-related endophthalmitis may lead to severe vision loss, even with prompt and appropriate treatment. Aqueous tap had a higher culture yield than needle vitreous tap in our series.