Purpose: To evaluate the outcomes of small-incision deep lamellar endothelial keratoplasty (DLEK) for the treatment of endothelial dysfunction at up to 5 years of follow-up. Design: Prospective, noncomparative case series. Participants: Sixty eyes of 55 consecutive patients who had corneal edema as a result of Fuchs' dystrophy, pseudophakic bullous keratopathy, bullous keratopathy secondary to glaucoma tube placement, failed graft, or deep endothelial scar. Methods: Patients underwent DLEK surgery at the Toronto Western Hospital. Main Outcomes Measures: Best spectacle-corrected visual acuity (BSCVA), manifest refraction, corneal endothelial cell density (ECD), and postoperative complications. Results: Data were available for 57, 49, 46, 23, and 7 eyes for examination at 1, 2, 3, 4, and 5 years, respectively. The mean spherical equivalent and refractive astigmatism were -0.18±1.62 diopters (D) and 1.67±1.36 D, respectively, at 1 year after surgery and remained stable at 2, 3, and 4 years after DLEK. Eliminating eyes with known significant macular or optic nerve disease, BSCVA of 20/188.5 before surgery improved to 20/56.9 at 1 year after surgery (P = 0.0002) and remained stable with BSCVA of 20/52.3, 20/46.2, and 20/56.8 at 2, 3, and 4 years, respectively, (P = 0.59, P = 0.31, P = 0.24, respectively). The number of patients who achieved 20/40 or better visual acuity, increased from a preoperative level of 13.5% to 44.1%, to 40%, to 48.4%, and to 50% at 1, 2, 3, and 4 years after surgery, respectively. The mean donor ECD before surgery was 2762±536 cells/mm2 and decreased by 43% at 1 year after surgery (1604±787 cells/mm2; P<0.0001), an additional yearly decrease by 14% (1257± 684 cells/mm2; P = 0.03), by 4% (1136±613 cells/mm2; P = 0.41), and by 1% (1064±515 cells/mm2; P = 0.68) was found at 2, 3, and 4 years, respectively. Complications included 4 graft dislocations, 2 primary graft failures, 5 rejections, and 12 secondary failures, with 27.5% graft failure at 4 years. Conclusions: Small-incision DLEK provides good and stable refractive and visual outcomes. The accelerated endothelial cell loss reported during the first 2 years after DLEK was shown to decrease and stabilize at low rates during the longer-term follow-up, which reduces the concern about progressive cell loss and secondary late endothelial failure. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.