Background: Trophic ulcers in leprosy patients pose a significant challenge to effective wound management due to impaired healing mechanisms and chronic inflammation. Platelet-Rich Fibrin (PRF), a biomaterial derived from autologous blood, has shown potential in enhancing wound healing. This study evaluates the efficacy of PRF in the management of trophic ulcers associated with leprosy. Materials and Methods: A prospective, interventional study was conducted on 50 leprosy patients with trophic ulcers, randomly divided into two groups: Group A (PRF-treated) and Group B (standard care). PRF was prepared using centrifugation of venous blood and applied directly to ulcers in Group A, while Group B received saline dressings and conventional wound care. Wound size, depth, exudate level, and healing rate were assessed at baseline, 4 weeks, and 8 weeks. Statistical analysis was performed using paired t-tests and chi-square tests. Results: The mean wound size reduction in Group A was 45% at 4 weeks and 72% at 8 weeks, significantly higher than Group B, which showed a reduction of 20% and 38% at the same intervals (p < 0.05). Complete healing was observed in 60% of ulcers in Group A by 8 weeks, compared to 30% in Group B. PRF application also reduced exudate levels and enhanced granulation tissue formation, with patient-reported pain scores significantly lower in the PRF group (mean reduction: 3.2 vs. 1.5; p < 0.01). Conclusion: PRF demonstrates significant potential in accelerating healing and improving outcomes in trophic ulcers of leprosy patients. Its autologous nature and cost-effectiveness make it a viable alternative to conventional wound management strategies. Further research with larger sample sizes is recommended to validate these findings.