BACKGROUND The current study was performed to report the long‐term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery and adjuvant radiotherapy (RT) in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma. METHODS Patients with stage III/IV resectable head and neck squamous cell carcinoma were randomized to surgery followed by RT or CCRT. The trial was halted prematurely due to poor accrual. Human papillomavirus status was tested on archival material using polymerase chain reaction sequencing. RESULTS Of the total of 119 patients, 60 patients were randomized to primary surgery (S arm) and 59 patients were randomized to CCRT (C arm). Human papillomavirus status was tested in 75 patients, and only 3 were found to be positive. The median follow‐up for surviving patients was 13 years. Analysis of the entire cohort demonstrated no statistically significant difference in overall survival and disease‐specific survival (DSS): 5‐year rates were 45% versus 35% for overall survival (P = .262) and 56% versus 46% for DSS (P = .637) for the S arm and C arm, respectively. Analysis by subsites indicated that this difference favoring the S arm was mainly driven by survival data among patients with cancers of the oral cavity and maxillary sinus. For patients with oral cavity cancer, survival was significantly better in those who underwent primary surgery compared with CCRT; the 5‐year DSS rate was 68% versus 12% for the S arm and C arm, respectively (P = .038). For patients with cancers of the maxillary sinus, the 5‐year DSS rate was 71% for patients on the S arm and 0% for patients on the C arm (P = .05). CONCLUSIONS These long‐term results demonstrate a significant advantage for primary surgery in patients with cancers of the oral cavity or maxillary sinus, providing strong support for primary surgery as the main modality of treatment for these subsites. In other subsites, CCRT and surgery with adjuvant RT were found to demonstrate similar efficacy for survival in patients with advanced resectable tumors. Cancer 2015;121:1599–1607. © 2015 American Cancer Society. The 10‐year update of a trial comparing concurrent chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic head and neck squamous cell carcinoma is presented. Subset analysis demonstrates that surgery with adjuvant radiotherapy is superior to concurrent chemotherapy and radiotherapy in patients with advanced resectable squamous cell carcinoma arising from the oral cavity and maxillary sinus.