EORTC protocol 22791 compared once daily fractionation (CF) of 70 Gy in 35–40 fractions in 7–8 weeks, to pure hyperfractionation (HF) of 80.5 Gy in 70 fractions in 7 weeks using 2 fractions of 1.15 Gy per day, in T 2–T 3 oropharyngeal carcinoma (excluding base of tongue), N 0, N 1 of less than 3 cm. From 1980 to 1987, 356 patients were entered. In the final analysis (June 1990), the local control was significantly higher ( p = 0.02 log-rank) after HF compared with CF. At 5 years, 59% of patients are local disease-free in the HF arm compared to 40 % in the CF arm. The superiority of HF was demonstrated in patients staged T 3N 0, T 3N 1 but not in T 2. The Cox model confirmed that the treatment regimen was an independent significant prognostic factor for locoregional control ( p = 0.007 log-rank). This improvement of locoregional control was responsible for a trend to an improved survival ( p = 0.08 log-rank). There was no difference in late normal tissue damage between the two treatment modalities.