There is very little published information comparing split-course and continuous-course irradiation in the adjuvant setting. To evaluate this issue, a retrospective analysis was performed of 161 patients with squamous cell carcinoma of the head and neck who received split-course (27 patients) or continuous-course (134 patients) irradiation following radical surgical resection. At 5 years, the actuarial rate of disease control above the clavicles for continuous-course irradiation was 80% versus 44% for split course (p = .002). Stratification of patients by primary site, surgical margin, AJCC stage, and tumor dose revealed a statistically significant (p less than or equal to .05) advantage in most of the subgroups for patients treated with continuous-course irradiation. The overall and cause-specific survival rates were also much better for patients treated with continuous-course irradiation, and the difference was highly statistically significant (overall 5-year survival, continuous course, 33%; split course, 15% [p = .005]; cause-specific 5-year survival, continuous course, 57%; split course, 37% [p less than .001]). A stepwise multivariate analysis confirmed that the type of irradiation course (continuous vs. split) was an independent prognostic variable of statistical significance for both control of disease above the clavicles and death with cancer present, with the split-course patients having worse results in both categories. The incidence of acute intolerance (4%) and late complications (7%) was the same in both the split- and continuous-course groups. As has previously been reported from this institution for patients treated with irradiation alone, these results demonstrate that in the postoperative setting, split-course irradiation yields lower local-regional control and survival rates compared with continuous-course therapy with no difference in the rate of severe complications. It is therefore recommended that split-course irradiation as used in this series be avoided whenever possible in patients with squamous cell carcinoma of the head and neck.