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To compare the frequency of rejection episodes and graft failure because of surgical complications or rejection after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for Fuchs endothelial dystrophy.A total of 201 eyes of 201 consecutive patients with Fuchs endothelial dystrophy undergoing keratoplasty were included. One hundred two patients underwent DSAEK and 99 PK in the period January 1, 2000, to December 31, 2010. Postoperative topical steroid treatment was similar in the 2 groups. Most patients in the PK group received a short course of oral prednisolone, which was not prescribed for patients undergoing DSAEK. Patient records were retrospectively reviewed; rejection episodes and causes of graft failures were recorded, and Kaplan–Meier survival curves up to 5 years after surgery were computed and compared.All rejection episodes and most graft failures occurred during the first 2 years after surgery. In this period, rejection episodes were noted in 16% of PK and in 5% of DSAEK-treated eyes (P = 0.03). During the first 5 years, significantly more DSAEK grafts than PK grafts had failed (P = 0.04) but only 2 PK-treated and no DSAEK-treated grafts failed because of rejection.The frequency of graft rejection episodes is higher after PK than DSAEK for primary endothelial disease, despite the use of oral prednisolone in the PK group. Early graft failure is more common after DSAEK than after PK, whereas graft failure because of previous rejection episodes is uncommon after DSAEK and PK.