Purpose: To report the first case of endophthalmitis after Descemet's stripping with automated endothelial keratoplasty caused by Mycobacterium abscessus. Methods: Observational case report. Results: An immunocompetent 88-year-old woman presented with endophthalmitis 2 months after a routine Descemet's stripping with automated endothelial keratoplasty resulting in decreased visual acuity and persistent vitreous opacities despite aggressive medical treatment. She underwent eventual pars plana vitrectomy with explantation of the posterior chamber intraocular lens and tube shunt. Operative cultures isolated Mycobacterium abscessus. With continued antibiotic therapy, the endophthalmitis eventually resolved with significant improvement of visual acuity. Conclusions: We report a case of endophthalmitis as a complication of Descemet's stripping with automated endothelial keratoplasty. Although a rare pathogen in endophthalmitis, M. abscessus is difficult to culture and treat. Surgical hypotony combined with contamination of intraoperative materials and/or postsurgical drops are the likely mechanisms of infection.