OBJECTIVES: To perform a comparative cost-effectiveness analysis of Descemet's stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for corneal endothelial disease. METHODS: Systematic review of the peer-reviewed English literature through a search of PubMed to populate a 5 year model of a) quality adjusted life years (QALYs) associated with clinical outcomes of the relatively new DSAEK procedure and the long-established PK procedure, and b) third party payer (US Medicare 2010) costs associated with associated medical, surgical and pharmaceutical services. RESULTS: Five year follow-up focusing on standard therapy and complications yeilds 2.99 QALYs associated with DSEAK and 1.94 QALYs with PK, a difference of 1.05.  Following slightly higher sugical costs of $US7925 for DSEAK and $US7544 for PK, total five year costs are $US10,104 associated with DSEAK and $US9840 with PK, a difference of $US264.  The ICUR is $US251.  Sensitivity analyses of differeing disc dislocation rates, astigmtism complication rates and cost parameters yield ICURs in the range of $US0 to $US500. CONCLUSIONS: Using the literature on outcomes and costs for treatments of corneal endothelial disease, a five year model yields robust results siggesting that DSEAK is slightly more expensive procedure than PK to third party payers, but with favorable quality adjusted life year resulting making DSEAK a cost-effective option under all scenarios considered.