Purpose: The aim of this study was to assess quality of life (QoL) and obturator functioning in patients having undergone a maxillectomy as a tumor ablative resection and rehabilitation with a prosthetic obturator. Materials and Methods: The University of Washington Quality of Life scale version 4 (UW-QoLv4) and the Obturator Functioning Scale (OFS) were used to evaluate the self-reported QoL and obturator functioning. The effects of demographic and treatment variables on QoL were assessed using age, defect size, postoperative radiotherapy (RT), neck dissection, and dentition. Results: The study included 16 men and 13 women with a mean age of 48.8 years. Of the 29 patients, 16 had a Brown Class 2a or smaller defect and 13 had a Brown Class 2b or larger defect. The mean OFS score (P = .004) and the physical (P = .001) and social-emotional function scores (P = .001) of the patients who received postoperative RT were significantly lower than those who did not receive postoperative RT. The subscales for swallowing (P = .008), saliva (P = .001), pain (P = .001), and shoulder function (P = .002) correlated strongly with postoperative RT on the UW-QoL. The subscales for pronunciation (P = .007) and saliva (P = .002) correlated significantly with RT on the OFS. The mean OFS scores were significantly lower for the patients with a Brown Class 2a or smaller defect than for Brown Class 2b or larger (P = .005). Conclusion: Postoperative RT was the strongest variable affecting QoL in patients with maxillectomy and prosthetic obturator reconstruction. The size of the defect slightly influenced the obturator function; however, it did not influence the overall QoL.