Patient compliance with the increasingly complex adjuvant therapy protocols has always been of concern, particularly in the head and neck cancer population. The Head and Neck Intergroup recently concluded a phase I11 prospective randomized trial testing the addition of three courses of cisplatinum containing combination chemotherapy to standard treatment defined as surgery and postoperative radiotherapy for advanced stage I11 and IV squamous cell carcinoma. The chemotherapy was administered following the surgery prior to the postoperative radiotherapy. Variation from protocol is ranked retrospectively as minor acceptable, major acceptable, and major unacceptable. The incidence of major unacceptable variation from the protocol for radiotherapy immediately following the surgery was 15% vs. 19% in the population that completed all three courses of the chemotherapy (P < 0.10). However, for those patients that completed less than the three courses of chemotherapy, the incidence of major unacceptable variation in radiotherapy was 33% (P < 0.001). This observation was controlled for site, stage, performance status, age, sex, surgical margins and experience of participating institution. We conclude that compliance with a multicourse adjuvant chemotherapy regimen is predictive of subsequent compliance to radiotherapy in the head and neck cancer population.