Background: The rise of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is changing current treatment paradigms. While significant efforts have been directed at treatment de-intensification and risk stratification, few have re-examined current surveillance strategies and none, to our knowledge, from a cost perspective. This study aims to compare cost per recurrence or distant metastasis detected between HPV negative and HPV positive OPSCC. Methods: A Markov transition model was created to model the National Comprehensive Cancer Network (NCCN) surveillance recommendations with a five-year time horizon from a Medicare perspective. Probabilities of detecting clinical recurrence for HPV negative and HPV positive OPSCC were derived from published literature. A standard discounting rate of 3% was used. Costs data was derived from the 4^th edition of the Center for Medicare and Medical Services Fee Schedule. A theoretical cohort of 16,400 HPV-positive OPSCC and 6,500 HPV-negative OPSCC patients treated with in the United States was used. Results: The cost of surveillance of our theoretical cohort over the first five years post-treatment is $142,331,259 ($122,526,531 for HPV positive OPSCC and $37,796,725 for HPV negative OPSCC). Each HPV positive recurrence detected costs $24,708 as compared to $11,337 for each HPV negative recurrence identified. Each distant metastasis diagnosed costs $10,523 in HPV positive disease compared to $8,658 in HPV negative disease. Deterministic sensitivity analyses varying cost of work-up, effectiveness of salvage treatment, and starting case mix did not significantly vary the cost differential between HPV positive and HPV negative disease. Conclusions: It costs twice as much to identify an HPV positive recurrence as it does for HPV negative disease. It is also more expensive to identify each distant metastasis in this subgroup. Furthermore, risk of second primaries as well as recurrence patterns differ significantly between HPV positive and HPV negative OPSCC patients. Our current surveillance paradigm is not well-tailored to HPV positive OPSCC and an alternative schedule should be considered and assessed.