Objective: To determine differences in quality of life (QOL) between patients with head and neck cancer who receive chemoradiation versus chemoradiation and neck dissection. Methods: A prospective cohort study was conducted at two tertiary otolaryngology clinics and a Veterans Administration hospital. Sample: 103 oropharyngeal patients with Stage IV squamous cell carcinoma treated via chemoradiation ± neck dissection. Intervention: self-administered health survey to collect health, demographic, and QOL information pretreatment and 1 year later. Main outcome measures: QOL via SF-36 and HNQoL. Descriptive statistics were calculated for health/clinical characteristics, demographics, and QOL scores. t tests evaluated changes in QOL over time. Results: Sixty-five patients underwent chemoradiation and 38 patients underwent chemoradiation and neck dissection. Only the pain index of the SF-36 showed a significant difference between groups (P < 0.05) with the neck dissection group reporting greater pain. Conclusions: After post-treatment neck dissection, patients experience statistically significant decrement in bodily pain domain scores, but other QOL scores are similar to those of patients who underwent chemoradiation alone.