To present long-term results of a randomized clinical trial on postoperative continuous 7-days-a-week radiotherapy in high-risk squamous cancer of the head and neck. Between 2001 and 2004, 279 patients with high-risk squamous cell cancer of the larynx (158 patients.) or cancer of the oral cavity/oropharynx (121 patients.) were enrolled. They were stratified according to the primary cancer site (larynx vs. others) and the treating center (Gliwice vs. Bydgoszcz) and randomized to receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 patients: p-CF) or 7-days-a-week (139 patients: p-CAIR). The analysis of loco-regional tumor control was a primary endpoint of the trial. Survival curves were compared using log-rank test. Hazard rates were estimated using Cox regression model. Two hundred seventy-five patients were eligible for the analysis (98.9%). Acute mucosal reactions were more severe in p-CAIR as compared to p-CF, and this transformed into higher peak incidence of Grade >1 subcutaneous fibrosis (38% vs. 27%), bone necrosis (9% vs. 2%) and xerostomia (43% vs. 28%). Some of these reactions subsided, however, with time. Seven-year loco-regional tumor control was 60.9% in p-CF vs. 65.7% in p-CAIR, the difference did not appear statistically significant (p = 0.67, RR = 0.92, 95% CI, 0.60-1.39). There were also no significant differences in 7-year metastases-free survival (88.3% vs. 84.9%) and second cancer-free survival (82.7% vs. 85.5%) for p-CF vs. p-CAIR, respectively. A trend toward improvement from p-CAIR was apparent for 7-year local control (68.7% in p-CF vs. 79.8% in p-CAIR, p = 0.28, RR = 0.76) as opposed to nodal control (79.5% in p-CF vs. 81.1% in p-CAIR, p = 0.95, RR = 0.98). Also, there was a strong trend toward improvement in 7-year LRC from p-CAIR among the patients with cancer of the oral cavity/oropharynx (51.8% vs. 67.7%, p = 0.10, RR = 0.60) as opposed to the patients with cancer of the larynx (67.0% vs. 64.3, p = 0.34, RR = 1.33). Seven-year overall survival did not significantly differ between the groups (30.6% p-CF vs. 35.7 p-CAIR, p = 0.56, RR = 0.91, 95% CI 0.68-1.23). A crude rate of distant metastases and second cancer was 18.5% (51/275) becoming, thus, a competitive cause of treatment failure as compared to loco-regional recurrences (89/275 = 32.4%). This study did not show significant improvement in LRC from shortening the overall radiation treatment time in a group of patients treated with postoperative radiotherapy for high-risk squamous-cell cancer of the head and neck. A trend toward such improvement was, however, noticeable in a subset of patients with cancer of the oral cavity/oropharynx.