Background: Both free posterior tibial flap (FPTF) and free radial forearm flap (FRFF) are commonly used for head and neck defects. They have many similarities in embryology, histology, and anatomy, but their advantages and disadvantages in head and neck repair have not been fully recognized. This study aimed to compare the cadaveric anatomy and clinical application of FPTF and FRFF for the reconstruction of head and neck defects after tumor resection. Methods: Anatomical dissection was performed on 10 fresh adult cadavers. The general characteristics of both flaps and the sites of recipients and donors were collected. A total of 31 and 25 patients underwent FPTF and FRFF construction, respectively. The patient medical records were assessed to obtain the clinical characteristics. Characteristics of the flap such as size, pedicle length, and clinical process data were collected and compared. The appearance, sensory disturbance, and effect on quality of life and daily activity were evaluated. Results: The posterior tibial artery was present and observed in all patients. The posterior vascular pedicle was longer than the radial artery. There was no difference between the diameters of arteries of FPTF and FRFF; however, the diameters of their veins differed. In terms of flap characteristics, FPTF was significantly larger and had a longer vascular pedicle than FRFF (40.68 +/- 11.07 vs. 53.77 +/- 29.02 cm2, P=0.03; 8.48 +/- 1.66 vs. 11.10 +/- 2.39 cm, P=0.00). Patients in the FPTF group had a significantly shorter total hospital stay (FRFF: 26.48 +/- 8.33 d; FPTF: 18.58 +/- 6.68 d), postoperative hospital stay (FRFF: 17.60 +/- 5.53 d; FPTF: 10.94 +/- 3.62 d), and flap harvest time (FRFF: 87.00 +/- 20.92 min; FPTF: 65.00 +/- 17.56 min) than FRFF group. There were far more complications of the donor site in the FRFF group than in the FPTF group. Also, according to the patients' subjective evaluations of the donor site, FPTF was superior to FRFF (P=0.00). Conclusions: FPTF is a reliable alternative to FRFF for head and neck reconstruction. These techniques share similar certain embryogenesis and anatomical characteristics but FPTF possesses unique aesthetic and clinical application advantages.