Fifty-one pairs of corneas, stored in either K-Sol or CSM (chondroitin sulfate corneal storage medium) from 8 to 97 hours (mean +/- standard deviation, 58 +/- 21 and 57 +/- 21 hours, respectively), were transplanted in a prospective, randomized manner into 99 patients (n = 102 eyes), paired by diagnostic group and procedure. Ninety-six percent of K-Sol grafts (n = 51) and 94% of the CSM grafts (n = 51) were clear at 6 months; 92% of both the K-Sol (n = 38) and CSM (n = 35) grafts were clear at 12 months. One primary donor failure occurred, a K-Sol cornea stored for 76 hours. The CSM group experienced a greater number of persistent epithelial defects beyond 2 weeks (7 versus 4 defects) and graft reaction episodes (7 versus 3 episodes) than the K-Sol group; however, an equal number of late graft failures (3) occurred in both groups. No significant differences by paired t test analyses were found in endothelial cell density, area, coefficient of variation, or figure coefficient at 3 (n = 37 pairs), 6 (n = 36 pairs), and 12 (n = 26 pairs) months between the two groups. Mean endothelial cell density significantly decreased by 11% +/- 22 by 3 months in the K-Sol group, whereas the 7% +/- 24 decrease in the CSM group was insignificant. By 12 months, both groups experienced a significant decrease: K-Sol, 27% +/- 22; CSM, 17% +/- 26. A significant decrease in the mean coefficient of variation (polymegathism) was noted after 3 months in the K-Sol group which returned to the preoperative mean by 1 year, whereas this parameter remained unchanged in the CSM group. Both chondroitin sulfate-based media result in successful corneal transplantation with storage up to 4 days; however, endothelial survival with both media are comparable with previous studies with McCarey-Kaufman (M-K) medium.