PURPOSE: To compare the quality of vision (straylight and contrast sensitivity) after femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS DSEK) and penetrating keratoplasty (PK). DESIGN: Prospective, randomized clinical trial. METHODS: SETTING: Multicenter (5 ophthalmic centers in The Netherlands). STUDY POPULATION: Eighty eyes of 80 patients with corneal endothelial dysfunction were included and were randomized to FS DSEK or PK. OBSERVATION PROCEDURES: FS DSEK and PK. MAIN OUTCOME MEASURES: Stray light, contrast sensitivity, astigmatism, uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), and visual symptom score. RESULTS: Stray light at 12 months was 1.37 +/- 0.2 logarithm of straylight for FS DSEK and 1.46 +/- 0.2 logarithm of straylight for PK (P = .151). During 12 months of follow-up, there was a significant improvement of straylight and contrast sensitivity after FS DSEK (P <.001) and PK (P <.001). The change of straylight and contrast sensitivity correlated significantly with the change of BSCVA after FS DSEK (r = -0.645; r = 0.580) and PK (r = -0.370; r = 0.659). The visual symptom score was comparable between the 2 groups during the 12 months of follow-up. CONCLUSIONS: Improvement of straylight and contrast sensitivity was significantly correlated with an improvement of BSCVA. Stray light and contrast sensitivity were improved significantly after FS DSEK and were comparable with those after PK, although BSCVA was slightly better in the PK group. (Am J Ophthalmol 2011;152:556-566.