The study compared proton radiotherapy (IMPT) with photon radiotherapy (IMRT) in patients with oropharyngeal cancer in a randomized multicenter phase 3, open-label, non-inferiority trial in the US. IMPT demonstrated non-inferiority to IMRT in terms of progression-free survival. At the same time, better overall survival was noted with IMPT compared to IMRT. Disease control (the ability to keep the tumor under control) was similar with both methods. However, IMPT resulted in a lower incidence of serious (high-grade) adverse events than IMRT. Treatment-related deaths and deaths after disease progression occurred more frequently with IMRT than with IMPT. Based on these results, IMPT is presented as a new standard treatment option for patients with oropharyngeal cancer.