The purpose of this study was to determine whether the full thickness macular hole (FTMH) closure rate with nonsupine positioning (NSP) is noninferior to the high closure rate achievable with face down positioning (FDP). All patients were pseudophakic pre macular hole repair. Final analysis consisted of 68 participants. Patients in the FDP group were instructed to maintain a face-down position for 10 hours / day for three full days (in total 30 hours of FDP during the first 72 postoperative hours). Patients in the NSP group were instructed to maintain a forward or slightly downward gaze. All patients were asked to avoid looking up during the daytime and avoid the supine position at night. After three postoperative days (72 hours), patient positioning was no longer required. Thirty-four patients were randomly allocated to either group. Final analysis of 68 patients demonstrated equal closure rates in the FDP and NSP groups, 33 closed FTMHs out of 34 (97.1%, 95% CI: 84.7–99.9) and confirmed our hypothesis that NSP is non-inferior compared with FDP. Similar closure rates were achieved in the >=400-µm FTMH subgroup, 93.8% (95% CI: 69.8–99.8) and 100.0% (95% CI: 83.9–100.0) in the FDP and NSP groups, respectively (P=0.43). Despite the high closure rate and the 95% CI above the noninferiority limit of 80% in the NSP group, the study was insufficiently powered to demonstrate noninferiority for the large FTMH subgroup. All Stage 4 FTMHs in both positioning groups closed. The authors suggest that gas fill above at least 65% on postoperative Day 4 reduces the risk of poor gas–macula contact and surgical failure.