Aim:To evaluate the clinical efficacy of Platelet Rich Fibrin (PRF) in the treatment of chronic ulcers of various etiologies with a focus on wound healing outcomes, microbial clearance, and overall patient response. Material and Methods:This single-centre, single-group, pre-post, prospective observational study was conducted in the Department of Surgery, LN Medical College, Bhopal, over a period of 6 months. A total of 30 patients aged ≥18 years with chronic leg ulcers (>4 weeks duration) of diabetic, venous, pressure, or traumatic origin were included. Patients with malignancy, autoimmune disorders, systemic infections, or on anticoagulant therapy were excluded. PRF was prepared using 20 ml of the patient’s venous blood centrifuged at 3000 rpm for 10 minutes. The PRF membrane was applied weekly under aseptic conditions for a maximum of 12 weeks. Wounds were evaluated weekly for reduction in size, granulation, epithelialization, and microbial presence. Results:Of the 30 enrolled patients, 22 (73.3%) were male and 8 (26.7%) female, with a mean age of 48 years. Diabetic ulcers were the most common (43.3%), followed by traumatic (23.3%), venous (20.0%), and arterial ulcers (13.3%). The average ulcer duration at baseline was 11 weeks. By the end of 12 weeks, complete wound closure was observed in 24 patients (80%), and 27 patients (90%) achieved >75% reduction in wound size. Two patients (6.7%) showed partial healing (25–50% reduction), while one patient (3.3%) had minimal response (<25% healing). The average healing time for complete epithelialization was 9 weeks. Microbial colonization was initially present in 19 patients (63.3%), but 73.7% of these became culture-negative after PRF application. Six patients with non-healing ulcers had comorbidities and persistent infection, particularly in arterial ulcers. Conclusion:PRF, with its unique three-layered fibrin-leukocyte matrix, demonstrated effective and well-tolerated healing in chronic ulcers. The treatment led to significant wound closure without the need for additional wound care measures in most cases. Healing outcomes were influenced by ulcer size, microbial burden, and underlying systemic conditions. PRF presents a clinically feasible, cost-effective, and biologically active approach in the management of chronic leg ulcers.