A novel autologous platelet-rich fibrin matrix membrane (PRFM) was assessed for the ability to facilitate healing in patients with chronic lower-extremity ulcers. Preliminary data are presented from a prospective trial (n=21). Twelve patients were identified with 17 venous leg ulcers (VLU) and nine bearing 13 nonvenous lower-extremity ulcers. Before enrollment, the patients were evaluated for vascular status and received appropriate surgical intervention to optimize arterial and venous circulatory status. None of the ulcers had responded to a variety of standard treatments from 4 months to 53 years. Initial ulcer size ranged from 0.7 to 65 cm2 (mean, 11.2 cm2). Each PRFM-treated patient received up to three applications of either a 35 or 50 mm fenestrated membrane, depending on initial ulcer size. The primary endpoints were percent and rate of complete closure as measured by digital photography, computerized planimetery, and clinical examination. Patients were followed weekly for 12 weeks with a follow-up visit at 16 weeks. At each 4-week interval, the extent of healing was assessed, and those patients with >50% reduction in wound area were allowed to continue to complete closure. Patients with <50% closure received repeated applications. Complete closure was achieved in 66.7% of the VLU patients (64.7% of treated ulcers) in 7.1 weeks (median, 6 weeks) with an average of two applications per patient. Forty-four percent complete closure was seen with non-VLU patients (31% of treated ulcers). From the results of this small-scale pilot study, PRFM shows significant potential for closing of chronic leg ulcers.