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Restoration of maxillary defects resulting from tumor ablative surgery presents a difficult challenge, with both functional and esthetic issues. Whether rehabilitation with an obturator prosthesis could significantly contribute to improved quality of life in patients with maxillary resection has been scarcely studied, with relatively small study samples.The purpose of this survey study was to assess the overall functioning of the obturator prosthesis and the effect of specific sociodemographic, medical, and treatment variables on obturator functioning and quality of life in patients with maxillectomy.Global quality of life (QOL) and satisfaction with the obturator prosthesis of 57 patients who underwent maxillectomy and prosthetic rehabilitation at the National and Kapodistrian University of Athens were assessed using 3 questionnaires: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30), the EORTC QLQ-HN35, and the obturator functioning scale. The data were analyzed using the Kruskal-Wallis 1-way ANOVA on ranks, hierarchical multiple regression analysis, and the Spearman rank order correlation (α=.05).Satisfactory functioning of the obturator prosthesis was the most significant predictor of improved QOL (P<.05). QOL was significantly related to additional treatments (P<.05), the size of the primary tumor (P<.05), and the size of the maxillectomy defect (P<.05). The most significant predictors of good obturator functioning were additional treatments (P<.01), age at the time of surgery (P<.05), presence of mandibular teeth (P<.05), and previous maxillary removable prosthetic experience (P<.05). Obturator functioning scale appearance and insertion subscales (r=0.47, P<.01), followed by speech (r=0.42, P<.01), were significantly related to better QOL.A well-functioning obturator prosthesis was the most significant determinant for improved QOL in patients with maxillary resection. Age at the time of surgery, adjuvant treatments, presence of mandibular teeth, and previous maxillary removable prosthetic experience were the most significant predictors for better obturator functioning, whereas the size of the maxillectomy defect had a significant effect on QOL but did not influence the functional outcome.