Purpose To report the 6- and 12-month results of the first United States clinical series of deep lamellar endothelial keratoplasty (DLEK) in the treatment of endothelial dysfunction. Design Prospective, noncomparative, interventional case series. Participants Eight eyes of eight patients with corneal edema from Fuchs’ dystrophy and pseudophakia. Methods A 9.0-mm limbal, scleral, partial-depth incision provided access for a deep lamellar corneal pocket dissection. A 7.5- to 8.0-mm posterior lamellar disc of recipient tissue was then excised and replaced through the pocket with a same size donor disc containing healthy endothelium. A temporary air bubble in the anterior chamber was used for donor tissue adherence, and no surface corneal incisions or sutures were necessary. Main outcome measures Preoperative and postoperative best spectacle-corrected visual acuity (BSCVA), manifest refraction astigmatism, TMS-1 topography, ultrasonic pachymetry, Orbscan topography, and endothelial cell density were evaluated. Intraoperative and postoperative complications are reported. Results At 6 and 12 months after surgery, all eight corneas were clear and the grafts were healed in good position. At 6 months, the BSCVA varied between 20/30 and 20/70, the average change in astigmatism from before surgery was +1.13 diopters (D; ±1.50 D), the average change in corneal power was −0.4 D (±1.7 D), the average pachymetry was 648 μm (±134 μm), and the average endothelial cell count was 2290 cells/mm 2 (±372 cells/mm 2). At 12 months, three of the four eyes reaching this time gate were 20/40 or better, with a change in astigmatism from before surgery of only +0.81 D (± 0.55 D), a corneal power change of −1.3 D (± 0.4 D), and an endothelial density of 2409 cells/mm 2 (± 154 cells/mm 2). One of the original nine eyes entered into this study required conversion to standard penetrating keratoplasty as a result of a microperforation during recipient pocket dissection and has experienced no ill effects. Conclusions The DLEK procedure, with its absence of corneal surface incisions and sutures, is a safe procedure that preserves the normal corneal topography, minimizes astigmatism and corneal power changes, and provides a healthy donor endothelial cell count and function. If interface optical clarity can be maintained, then this technique offers considerable advantages over penetrating keratoplasty in the treatment of endothelial dysfunction.