Alveolar ostitis (AO) is the dissolution of blood clot due to enhanced local fibrinolysis and is caused by trauma to the jaw (direct) or because of bacterial involvement (indirect), which result in the activation of plasminogen pathway. Platelet-rich fibrin (PRF) is a platelet concentrate that comprises numerous autologous growth factors, and immune cells hence has the potential to expedite the healing process. The objective of the study was to determine the efficacy of PRF in the surgically extracted third molar in the context of its potential progress to AO. A total of 180 patients of 18-65 years with unilateral painful mandibular third molars due to caries, failed endodontics treatment, and pericoronitis were included in the study. Exclusion criteria were patients who were medically compromised, smokers, alcoholic, poor oral hygiene, third molar having associated periapical pathology, and receiving antibiotic regime in the last 2 weeks. Before starting surgical procedure, patients were randomly divided into two groups using lottery method. Group I received PRF in the extraction socket, while in Group II, the extraction site was left for normal healing as practiced in a standard procedure. Pain was assessed in terms of pain score, and it was recorded on a 10 mm visual analog scale on the first and third postoperative days. Mean age of the patients was 41.35 ± 9.87 years. The mean age in Group I was 42.84 ± 10.52 years, and in Group II, it was 40.54 ± 9.52 years. Out of 180 patients, 90 (50.0%) were male and 90 (50.0%) were female, with a male-to-female ratio of 1 : 1. Frequency of AO following mandibular third molar surgery in Group I receiving PRF was 2.22% and in non-PRF group 12.22% (p-value = 0.010). The incidence of AO following mandibular third molar surgery was lower when PRF was used.