center dot PURPOSE: To compare submandibular gland (SMG) transplantation with minor salivary gland (MSG) transplantation for the treatment of different dry eye diseases center dot DESIGN: Retrospective clinical cohort study.center dot METHODS: A total of 73 refractory DED eyes were divided into 3 groups. Group A comprised 35 end-stage DED eyes that underwent SMG transplantation. Group B comprised 20 end-stage DED eyes with MSG transplantation. Group C comprised 18 non -end-stage DED eyes with MSG transplantation. Schirmer test (ST), tear break-up time (TBUT), corneal fluorescein staining (FL), and best-corrected visual acuity (BCVA) were measured before and after surgery.center dot RESULTS: Hospital length of stay, length of operation, and hospital fee were significantly higher in group A than in group B or C. Eyes in group A showed the most severe DED disease, with preoperative ST, TBUT, FL, and BCVA of 0.36 mm per 5 minutes, 0.03 seconds, 10.97, and 0.11, respectively, which improved significantly to 20.23 mm per 5minutes, 1.74 seconds, 7.58, and 0.2 at > 2-year follow-up. Group B had similar baseline data, and significant but limited improvement only in the ST (0.55 mm per 5 minutes to 3.79 mm per 5 minutes) and FL (11.10 to 9.58) after the operation. Group C had better baseline ST, TBUT, FL, and BCVA of 0.89 mm per 5min, 3.49 seconds, 1.83, and 0.81, respectively, which improved significantly (except for BCVA) to 9.35 mm per 5min, 9.08 s, 0.53, and 0.89 after MSG transplantation.center dot CONCLUSION: SMG transplantation could be recommended to treat end-stage refractory DED. MSG transplantation may provide satisfying results for refractory DED with relatively less severe impairment of the eye. (Am J Ophthalmol 2022;241: 238-247.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NCND license ( http://creativecommons.org/licenses/by-ncnd/4.0/ ))