PURPOSE: To describe and compare the histological changes in the cut edges of the remaining donor corneal rim using femtosecond laser-assisted keratoplasty (FAK) versus conventional penetrating keratoplasty (PK) via light and transmission electron microscopic examination. METHODS: This was a prospective observational study of 10 eyes; 5 FAK (top-hat technique) and 5 conventional PK. Main outcomes were histological findings at the cut edge of the donor corneal rim (at 3, 6, 9, and 12 o'clock). RESULTS: Cellular and ultra-cellular changes in the form of stromal edema, disorganized collagen fibers, and nuclear changes were more prominent in the FAK eyes as compared to the conventional PK ones. CONCLUSION: FAK induces more collateral damage in the cut edge of corneal donor graft at cellular and ultra-cellular levels, compared to conventional trephination. Further studies are required to investigate the clinical ramifications of this observation.