Introduction Nonhealing ulcers have a huge burden on the patient, by having high morbidity in terms of chronic pain, partial or complete loss of function, mental health issues, and social isolation, and can have a massive financial burden on the patient. Various novel therapies have been developed to treat nonhealing ulcers. Platelet-rich fibrin (PRF) has been developed in the recent era initially in the dental world for treating oral ulcers. Now, the role of PRF is strongly established in treating nonhealing ulcers. PRF has an aggregate of a myriad of growth factors and cytokines that stimulate healing of the wounds. In this study, we have compared the efficacy of PRF in treating nonhealing ulcers of the lower limb against normal saline dressings. Aims and objectives This study aims to determine the efficacy of platelet-rich fibrin over normal saline dressings in the treatment of nonhealing ulcers of the lower limb by comparing the percentage reduction in the surface area of wounds after treatment in both groups. Methods Fifty patients with nonhealing ulcers were selected and randomly divided into two groups with 25 patients in each group. Cases were treated with PRF dressings weekly for a period of six weeks. Controls were treated with normal saline dressings weekly for a period of six weeks. The percentage reduction in the size of the ulcer after treatment was recorded in both groups and compared. Patients of age 18-60 with nonhealing ulcers of the lower limb of >12 weeks duration have been included in the study. Patients having wounds with active infection, wound size > 35 cm, uncontrolled diabetes, peripheral vascular disease with Ankle-Brachial Index < 0.9, osteomyelitis of the underlying bone, and immunocompromised state, and patients on antiplatelet drugs have been excluded from the study. Results The mean age of the patients included in the study was 42.88 ± 2.73 years. The mean initial surface of the woundwas 14.95± 3.08 cmamong cases and 13.28 ± 2.83 cm among controls. The mean surface area of the wound after six weeks was 1.59 ± 0.78 cm among cases and 11.08 ± 2.74 cm among controls. The mean percentage reduction in the wound size after six weeks of treatment was 89.3% among cases and is significantly higher than in the normal saline group (16.5%) (Mdn = 14.63, U = 23, p < 0.00001). Conclusion Platelet-rich fibrin is an emerging potential topical agent for the treatment of nonhealing ulcers of the lower limbs and is more effective than normal saline dressings and also has the advantage of being cost-effective.