Objectives/Hypothesis: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct clinical entity with good prognosis, unique demographics, and a trend toward treatment deintensification. Patients with this disease may opt out of recommended postoperative radiation therapy (PORT) for a variety of reasons. The aim of this paper was to examine factors that predict patient refusal of recommended PORT in HPV-associated OPSCC, and the association of refusal with overall survival.Study Design: Retrospective population-based cohort study of patients in the National Cancer Database.Methods: We conducted a retrospective cohort study of patients in the National Cancer Database diagnosed with OPSCC between January 2010 and December 2015. We primarily assessed overall survival and the odds of refusing PORT based on demographic, socioeconomic, and clinical factors. Analysis was conducted using multivariable logistic regression and multivariable Cox proportional hazards model.Results: A total of 4229 patients were included in the final analysis, with 156 (3.7%) patients opting out of recommended PORT. On multivariable analysis, patient refusal of PORT was independently associated with a variety of socioeconomic factors such as race, insurance status, comorbidity, treatment at a single facility, and margin status. Lastly, PORT refusal was associated with significantly lower overall survival compared to receipt of recommended PORT (hazard ratio 1.69, confidence interval 1.02-2.82).Conclusions: Patient refusal of recommended PORT in HPV-associated OPSCC is rare and associated with variety of disease and socioeconomic factors. PORT refusal may decrease overall survival in this population. Our findings may help clinicians when counseling patients and identifying those who may be more likely to opt out of recommended adjuvant therapy.