OBJECTIVE To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). METHODS Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. RESULTS Median follow-up was 3.4 years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively (p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021). Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p = 0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. CONCLUSIONS In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.