Background: This study aimed to determine whether, in eyes treated for macular hole by vitrectomy and autologous platelet injection, short-term tamponade with SF₆ gas was as effective as longer tamponade with C₃F₈ gas. Methods: Patients in group 1 (n=31) had vitrectomy, injection of platelet concentrate, and 16% C₃F₈ gas/air exchange. Patients in group 2 (n=31) were similarly treated, except that 23% SF₆ gas was used. Group 1 patients were required to posture prone for 2–4 weeks, group 2 for 6 days. Results: All patients had 3 months’ follow-up. Postoperatively, visual acuity improved faster in group 2. However, the final mean improvement in logMAR acuity was similar in both groups. Intraocular pressure (IOP) spikes occurred in 12 patients in group 2 and in 17 patients in group 1. Posterior subcapsular cataract (PSCC) occurred in 55% of cases in group 1 and in just 37% in group 2. The rate of anatomical success in group 1 was 96.7%, and in group 2, 93.5% (P=1.0). Conclusions: The combination of SF₆ gas, platelet concentrate, and short-term prone posturing gave a degree of anatomical and visual success comparable to that of the group which had longer tamponade. Although no differences were statistically significant, several trends did emerge; in group 2, patients recovered visual acuity faster, had fewer IOP spikes, and there were fewer cases of PSCC formation.