Objective Profunda femoris artery perforator flaps (PAPFs) have not been widely used in head and neck reconstructions. The feasibility and outcomes of PAPFs for various head and neck reconstructions need to be investigated. Study Design Retrospective analysis. Setting A single-institution review. Methods PAPFs were utilized in head and neck reconstructions from 2019 to 2021. Local anatomy, surgical technique, and complications were discussed. Chimeric PAPF applications with muscle components were described for coverage of extensive multiunit defects. Additionally, aesthetic and functional outcomes were compared with anterolateral thigh perforator flaps. Results A total of 33 cases were included. The average age was 54.2 years (range, 30-74). The most common underlying pathology was oral squamous cell carcinoma (n = 26, 78.8%), while the mean ± SD body mass index was 25.4 ± 2.8 kg/m2. Middle perforators (n = 14, 42.4%) were the most commonly utilized ones. The perforator-based chimeric/composite applications were used in 9 (27.3%), with the muscular components consisting of gracilis (n = 3, 9.1%), adductor magnus (n = 5, 15.2%), or semimembranosus muscles (n = 1, 3.0%). Venous thromboses of the PAPFs were found in 2 (6.1%), though salvaged. The occurrence of postoperative 90-day morbidity (complication) was related to mandibulectomy/maxillectomy ( P = .020). Postoperative validated questionnaires showed a trend of intermediate to high scores, indicating noninferior outcomes in several categories, when compared with the anterolateral thigh perforator flap counterparts. Conclusion PAPFs are a good reconstructive alternative for intermediate to large head and neck reconstructions. Besides, PAPFs can provide sufficient tissue volume and versatility of potentially incorporating adjacent muscle components.