PURPOSE. We compared the regeneration characteristics of injured corneal subbasal nerve fibers (CSNFs) and keratocyte reaction following LASIK with a femtosecond laser (FS-LASIK), One Use-Plus Sub-Bowman's keratomileusis (OUP-SBK), and M2 90 microkeratome to provide a more suitable treatment strategy. METHODS. A total of 22 eyes that underwent FS-LASIK, 32 eyes that underwent OUP-SBK, and 26 eyes that underwent conventional LASIK were analyzed by confocal microscopy. Morphologic modifications of corneal architecture were evaluated postsurgically at 1, 3, and 6 months, and comparisons were made by ANOVA analysis. RESULTS. The density of stromal keratocytes in the FS-LASIK group was higher than that of OUP-SBK and conventional LASIK groups at 1 month postsurgery (P < 0.05), while in the OUP-SBK group it was higher than that of the FS-LASIK and conventional LASIK groups at 3 months postsurgery (P < 0.05). Regeneration of CSNFs was detected in 90% of eyes in all three groups around 3 mm of the peripheral flap at 1 month postoperation. CSNFs in 6.3% of the eyes in the OUP-SBK group were even observed around the peripheral flap at 6 mm 3 months after surgery, CSNFs were found in 62.5% of eyes (conventional LASIK), 72% of eyes (OUP-SBK), and 64.3% of eyes (FS-LASIK) around 3 mm near the center of the flap. While at 6 months, CSNFs were found in 100% of the eyes in all three groups. CONCLUSIONS. Keratocyte reactions after FS-LASIK and OUP-SBK were a little more severe than that after conventional LASIK. The repairing velocity of subbasal nerve fibers in the OUP-SBK group was a little faster than that of the FS and conventional LASIK groups. (Invest Ophthalmol Vis Sci. 2012;53:5536-5544) DOI:10.1167/iovs.11-8786