Published in JAMA Network Open, this retrospective study included 292 patients with nonmetastatic oropharyngeal cancer (OPC) of which 272 [93%] were HPV–positive tumors. Fifty-eight patients (20%) were treated with IMPT and 234 (80%) with IMRT. With a median follow-up of 26 months, this study reported no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59); however, the incidence of acute toxicities and chronic xerostomia of grade ≥2 was significantly higher for IMRT compared with IMPT. The acute toxicities were recorded including oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P < .001), xerostomia of grade ≥2 (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade ≥2 (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade ≥3 (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade ≥2 (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade ≥2 (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects of grade ≥3. Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months. The findings suggest that IMPT should be considered as a potential primary radiotherapy modality for nonmetastatic OPC if available because IMPT was associated with fewer acute toxic effects compared with IMRT and with few chronic toxic effects. Oncologic outcomes were favorable in both groups, with 5% locoregional recurrence at 2 years with IMPT.