A multi-institutional cohort study of 240 patients with human papillomavirus–associated oropharyngeal carcinoma found that deintensified 60-Gy chemoradiotherapy was associated with low long-term locoregional recurrence rates in selected patients with favorable-risk disease. At 5 years, locoregional recurrence was 3.4%, progression-free survival was 86.5%, and overall survival was 92.4%. Nearly half of recurrences occurred more than 2 years following treatment, underscoring the importance of extended surveillance. The single-arm study does not establish equivalence to standard-dose therapy but supports ongoing investigation of treatment deintensification.