Objectives. To compare health-related quality of life measures after treatment for advanced (stages III and IV laryngeal and hypopharyngeal cancers. Study Design: Retrospective chart review and patient response to Health Status Questionnaire-12 (HSQ-12). Methods. Our study included 54 patients identified from the Tumor Registry of the University of Louisville Brown Cancer Center who were diagnosed and treated between 1995 and 2000. Demographics, tumor data, and treatment information were obtained from the Tumor Registry database. Questionnaires were mailed to all patients and included telephone followup. Comparative data and responses were analyzed for the 24 patients who responded to the survey. Results. Fifteen patients were treated with chemotherapy and radiation therapy (CRT). Six patients underwent surgery with postoperative radiation therapy (SRT). The remaining three patients were treated with radiation therapy but were not used in this analysis. The average follow-up was 35 months after treatment. The CRT and SRT groups were statistically similar regarding age, sex, duration of follow-up, tumor grade, and tumor stage. Laryngeal primary tumors were more common in the SRT group than in the CRT group (P =.005). Eight domains were assessed by the HSQ-12: physical functioning, role-physical, bodily pain, health perception, energy/fatigue, social functioning, role-mental, and mental health. No statistical differences were found between the CRT and SRT groups, except for role limitations attributable to physical health (P =.007). Conclusions. These results indicate that only one of eight domains differs significantly between treatment groups when using the HSQ-12. Two-year survival end-point analysis of global health assessment may represent a simplified and meaningful way to compare treatment modalities in patients with advanced-stage head and neck cancer.