Purpose <p>To evaluate and compare the outcomes of internal limiting membrane (ILM) flap and autologous whole blood application for treatment of complicated macular holes (CMHs).</p> Methods <p>A retrospective analysis of medical records was performed for patients who underwent vitrectomy for CMHs, including preoperative and postoperative evaluations at 1, 3, and 6 months. Patients were divided into two groups: Group 1 autologous whole blood and Group 2 ILM flap application. The hole parameters were measured using preoperative OCT images. The integrity of the external limiting membrane (ELM)-ellipsoid zone (EZ) and anatomical closure patterns was evaluated on postoperative OCT images. Closure patterns were scored.</p> Results <p>The study included 37 eyes: 17 (45.9%) in Group 1 and 20 (54.1%) in Group 2. The postoperative closure rate was 94.1% in Group 1 and 100% in Group 2, with an overall rate of 97.3%. No significant differences were found between Groups 1 and 2 in OCT parameters, best-corrected visual acuity, ELM–EZ recovery, or macular edema reduction at any follow-up time point (<i>p</i> &gt; 0.05). The optimal closure score was higher in group 2 at the first month postoperatively (<i>p</i> = 0.036), but no difference was detected at the third and sixth months (<i>p</i> = 0.870 and <i>p</i> = 0.780, respectively).</p> Conclusions <p>This study demonstrated that both autologous whole blood and ILM flap techniques are effective in the surgical management of CMHs, achieving high closure rates. Given its comparable postoperative results to the ILM flap, autologous whole blood may be a beneficial option in CMH surgery.</p>