Purpose: The aim of this study was to compare complication rates of Descemet membrane endothelial keratoplasty (DMEK) performed by directly supervised and nondirectly supervised corneal fellows. Methods: This study was a retrospective, comparative case series of DMEK surgeries performed by novice surgeons (less than 15 DMEK cases) with or without direct direct expert supervision. Patients who underwent surgery for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy with a minimum follow-up of 12 weeks were included. Data on patients’ demographics, surgical details, surgeon level, intraoperative and postoperative complications, and rate of rebubbling were collected. Results: In this study, 41 nondirectly supervised and 48 directly supervised DMEK surgeries were included. At 6 months, 67.4% of eyes achieved a best-corrected visual acuity of ≤0.3 logMAR with no significant difference between groups (P = 0.95). Intraoperative complications occurred in 22% of cases in the nondirect supervision group and 4.2% in the direct supervision group (P = 0.02). Postoperative complications occurred in 9.8% of cases in the nondirect supervision group and 6.2% of cases in the direct supervision group (P = 0.7). The rebubbling rate was comparable in the 2 groups (34.1% vs. 33.3%, P = 1.0). Five cases (12.2%), all from the nondirect supervision group, required secondary keratoplasty (P = 0.02). The overall complication rate was significantly higher in the nondirect supervision group (31.7% vs. 10.4%, P = 0.03). Conclusions: Functional success can be achieved in directly supervised or nondirectly supervised DMEK surgery. However, nondirectly supervised DMEK surgery may associate with higher rates of complications.