AIM: To investigate the impact of non-Descemet stripping endothelial keratoplasty (non-DSEK) on graft rejection rate, and its overall procedural effectiveness in patients. METHODS: Non-DSEK was performed on 65 eyes of 64 patients, and the procedural outcomes, including rejection episodes, failure and dislocation of the grafts, best corrected visual acuity (BCVA), endothelial cell density (ECD), and other complications, were analyzed retrospectively. RESULTS: Of the 65 eyes, 63 recovered from bullous keratopathy with a clear cornea. The mean follow-up time was 26.4mo (range, 6-84mo). The mean BCVA improved from 1.70 logMAR preoperatively to 0.54 logMAR at 3mo, 0.46 logMAR at 6mo, and 0.37 logMAR at 1y after surgery. The postoperative donor ECD of the 25 patients who successfully underwent specular microscopic examination was 1918±534 cells/mm2 (range, 637 to 3056 cells/mm2), and the mean endothelial cell loss was 41.9% at 24mo postoperatively. One eye developed secondary glaucoma and required regrafting via penetrating keratoplasty (PKP). Another eye had postoperative graft failure due to rejection at 26mo. Postoperative graft dislocation occurred in eight eyes. All of the eight dislocated grafts were reattached using air reinjection. CONCLUSION: Immunological graft rejection of the donor graft rarely occurs in non-DSEK. Therefore, non-DSEK is a safe, concise, and effective alternative to restore corneal decompensation when the Descemet membrane is disease-free.