Objective To introduce the technique and clinical application of free lobed anteromedial thigh perforator flap. MethodsBetween October 2017 and December 2021, 65 patients with buccal and oral cancer penetrating defects were planned to treat with free lobed anterolateral thigh flap transplantation, of which 15 cases were found that the sole anterolateral thigh perforator was actually a branch of the anteromedial thigh perforator, and then the free lobed anteromedial thigh perforator flap was harvested for repair. There were 12 males and 3 females with an average age of 34.6 years (range, 29-55 years). According to Union for International Cancer Control (UICC) TNM staging, there were 7 cases of T4N0M0, 4 cases of T4N1M0, 2 cases of T3N1M0, and 2 cases of T3N2M0. The disease duration was 1-10 months (mean, 6.3 months), and the area of secondary soft tissue defect left after radical resection of buccal and oral cancer was from 5 cm×4 cm to 10 cm×6 cm. The anterolateral thigh skin flap ranged from 5 cm×4 cm to 13 cm×6 cm, and the anteromedial thigh skin flap ranged from 5 cm×3 cm to 10 cm×6 cm. The free trilobed anteromedial thigh flap was prepared according to the actual branches of the main trunk of the anteromedial thigh perforator in 4 cases, and the vastus medialis muscle flap was used to fill the cavity defect of the floor of mouth in 7 cases. Among the 15 patients, the vessel pedicles of the anteromedial thigh perforators were derived from the main femoral artery and vein in 8 cases, from the main descending branch of the lateral femoral circumflex artery in 4 cases, and from the main lateral femoral circumflex artery in 3 cases. Results Hematoma occurred in 2 cases after operation, which was successfully saved after emergency exploration. No vascular crisis occurred, and partial necrosis of anterolateral femoral skin island occurred in 1 case, which was healed with debridement. The remaining flaps survived successfully, and the wounds and donor site incisions healed by first intention. All the patients were followed up 12-36 months (mean, 14.6 months). The appearance of the flap was satisfactory, and no obvious swelling was found; the mouth opening and language function were satisfactory; only linear scar was left in the donor area, and the thigh function was not significantly affected. Local recurrence occurred in 3 cases, and the defect after tumor resection was repaired with pedicled pectoralis major myocutaneous flap. Four patients with neck lymph node metastasis, including ipsilateral side in 3 patients and contralateral side in the other 1 patient, all underwent neck lymph node dissection again. The 3-year survival rate was 86.7% (13/15). Conclusion The anteromedial thigh perforator vessels distributed in the anterolateral region of the thigh can be used to prepare the anterolateral thigh split lobed flap to repair the buccal and oral cancer penetrating defects.