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ObjectivesThis study aimed to compare the quality of life (QOL) of patients, clinical results of the recipient site, and morbidities of the donor site between the use of free anterolateral thigh flaps (ALTFs) and radial forearm flaps (RFFs) for reconstruction of full cheek defects following tumor resection.Materials and methodsWe retrospectively reviewed 52 patients who underwent reconstruction of full cheek defects using free ALTFs and free RFFs following tumor ablation at our center. The range of mouth opening, speech, swallowing, facial appearance, donor site complications, and subjective symptoms based on the University of Washington Quality of Life (UW‐QOL) questionnaire findings were assessed in the ALTF and RFF groups at 3, 12, and 36 months after surgery.ResultsQuality of life, range of mouth opening, facial appearance, mood and anxiety, donor site appearance, subjective feeling, and functional impairment were better in the ALTF group than in the RFF group based on the physical examination findings and questionnaire scores.ConclusionThis study found better QOL and better functional results at the recipient site and minor morbidities at the donor site with the use of free ALTFs in the reconstruction of full cheek defects.