This study investigated the quality of life (QoL) of patients with head and neck cancer undergoing immediate reconstruction of the mandible with free fibula flap. From March 2006 to January 2011, the QoL of 42 patients was assessed using the Medical Outcomes Study Short Form 36 and the University of Washington QoL (version 4) questionnaires. The assessments were performed at least 24 months after surgery. A total of 31 of the 42 questionnaires (73.8%) were returned. The length of harvested fibula varied from 17.5 to 26.1 cm. In the Short Form 36, the lowest-scoring domain was vitality, whereas the highest scores occurred in physical role. According to the University of Washington QoL, the key domains affected by surgery are chewing, speech, and appearance. The domain of pain has the best score. There was a significant effect on the QoL of patients with head and neck cancer with resections of the mandible who had undergone free fibula flap reconstruction. Data from this study may provide useful information for physicians and patients, which may be of value during discussion of treatment modalities for head and neck cancers.