Objective: To review the published literature on safety and outcomes of Descemet's stripping endothelial keratoplasty (DSEK) for the surgical treatment of endothelial diseases of the cornea. Design: Peer-reviewed literature searches were conducted in PubMed and the Cochrane Library with the most recent search in February 2009. The searches yielded 2118 citations in English-language journals. The abstracts of these articles were reviewed and 131 articles were selected for possible clinical relevance, of which 34 were determined to be relevant to the assessment objectives. Results: The most common complications from DSEK among reviewed reports included posterior graft dislocations (mean, 14%; range, 0%-82%), followed by endothelial graft rejection (mean, 10%; range, 0%-45%), primary graft failure (mean, 5%; range, 0%-29%), and iatrogenic glaucoma (mean, 3%; range, 0%-15%). Average endothelial cell loss as measured by specular microscopy ranged from 25% to 54%, with an average cell loss of 37% at 6 months, and from 24% to 61%, with an average cell loss of 42% at 12 months. The average best-corrected Snellen visual acuity (mean, 9 months; range, 3-21 months) ranged from 20/34 to 20/66. A review of postoperative refractive results found induced hyperopia ranging from 0.7 to 1.5 diopters (D; mean, 1.1 D), with minimal induced astigmatism ranging from -0.4 to 0.6 D and a mean refractive shift of 0.11 D. A review of graft survival found that clear grafts at 1 year ranged from 55% to 100% (mean, 94%). Conclusions: The evidence reviewed is supportive of DSEK being a safe and effective treatment for endothelial diseases of the cornea. In terms of surgical risks, complication rates, graft survival (clarity), visual acuity, and endothelial cell loss, DSEK appears similar to penetrating keratoplasty (PK). It seems to be superior to PK in terms of earlier visual recovery, refractive stability, postoperative refractive outcomes, wound and suture-related complications, and intraoperative and late suprachoroidal hemorrhage risk. The most common complications of DSEK do not appear to be detrimental to the ultimate vision recovery in most cases. Long-term endothelial cell survival and the risk of late endothelial rejection are beyond the scope of this assessment. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.