The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.