Purpose: To determine roles of patient history, donor tissue characteristics, tissue preparation methods, and surgeon technique for graft detachment requiring rebubbling after Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures., Methods: Retrospective analysis of all eyes undergoing first-time DSAEK or DMEK at the study institution between 2013 and 2022. Data were collected regarding recipients' history, donors' medical history, tissue preparation methods, intraoperative details, and postoperative clinical outcomes. Multivariate statistical analysis was conducted to identify risk factors for graft detachment necessitating rebubbling., Results: Of 1240 eyes meeting inclusion criteria, 746 (60.2%) underwent DSAEK, and 494 (39.8%) underwent DMEK. DSAEK procedures had 12.5% rebubbling rate, whereas DMEK procedures had 18.4% rebubbling rate (P = 0.005). Sub50-DSAEK (<50 μm) grafts had 16.0% rebubble rate, whereas sub100-DSAEK (51-99 μm) and >100 μm DSAEKs had rebubble rate of 9.9% and 9.5%, respectively (P = 0.006). Significant risk factors for DSAEK graft detachment included history of retinal surgery (OR = 2.59), preloaded tissue (OR = 2.70), forceps insertion (OR = 2.33), use of sub50-DSAEK lenticules versus sub100-DSAEK (OR = 2.44) and >100 μm DSAEK (OR = 2.38) lenticules, and donor history of noninsulin-dependent diabetes mellitus (OR = 4.18). DMEK risk factors included recipient history of cancer (OR = 2.51) and use of higher SF6 gas concentration (OR = 1.09). Although rebubbled DMEK eyes had comparable refractive outcomes to nonrebubbled eyes (P >0.05), rebubbled DSAEK eyes had worse refractive outcomes at all time points (P < 0.05)., Conclusions: Graft detachments in DSAEK and DMEK are influenced by various factors, including donor tissue characteristics, tissue preparation, and surgical technique. Identifying and understanding these factors can potentially improve postoperative outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)