Background <p>Delayed or nonhealing wounds following surgery present a significant clinical challenge. Autologous epidermal cell regeneration technology has shown promise in enhancing wound healing. This study aimed to evaluate its efficacy in treating postoperative nonhealing wounds.</p> Methods <p>This randomized, controlled trial involved 151 patients with nonhealing postoperative wounds, randomly assigned to two groups: the experimental group (<i>n</i> = 75) received standard treatments combined with autologous epidermal cell regeneration technology, and the control group (<i>n</i> = 76) received standard treatments alone. The primary endpoint was wound healing at 3 weeks. Key secondary endpoints included time to complete healing and recurrence rate. Statistical tests were performed to determine the significance of differences between groups. The study was registered with UMIN-CTR (UMIN000056733).</p> Results <p>In the intention-to-treat population, significantly more patients in the experimental group achieved the primary endpoint at week 3 (66 of 75 [88.0%] vs. 51 of 76 [67.1%]; difference 20.9%, 97.5% CI: 0.0802, 0.3377; <i>p</i> = 0.004). Similar results were observed in the modified intention-to-treat population (62 of 71 [87.3%] vs. 47 of 73 [64.4.1%]; difference 22.9%, 97.5% CI: 0.0950, 0.3638; <i>p</i> = 0.003). These results were confirmed in the per-protocol population (61 of 68 [89.7%] vs. 47 of 69 [68.1%]; difference 21.6%, 97.5% CI: 0.0843, 0.3475, <i>p </i>= 0.004). In the safety analysis, 24.7% of the experimental group vs. 60.3% of the control group experienced treatment-emergent adverse events. The most common treatment-emergent adverse events were wound exudate and dehiscence, with no deaths or carcinogenicity reported.</p> Conclusion <p>Autologous epidermal cell regeneration technology is an effective and safe treatment for postoperative nonhealing wounds.</p>