Purpose: Many cases of postirradiation oral carcinoma have been reported, but its prognosis and optimal treatment modalities are not clear. Thus, the clinicopathologic characteristics and prognosis between postirradiation tongue squamous cell carcinoma (PTSCC) and primary tongue squamous cell carcinoma (TSCC) were compared. Patients and Methods: A retrospective cohort study was conducted to assess patients with PTSCC or TSCC. The primary predictor variable was tumor type. The primary outcome variable was prognosis, and the additional outcome variables were clinicopathologic characteristics. Survival analysis was performed, and Kaplan-Meier analysis was conducted to compare the effects of clinicopathologic factors on survival using SPSS 18.0. Moreover, the Cox model was applied in multivariate analysis. Results: The sample was composed of 449 patients with PTSCC (n = 68; 47 men and 21 women; age range, 31 to 72 yr) and TSCC (n = 381; 247 men and 134 women; age range, 20 to 86 yr). Patients with PTSCC were found to have a substantially poorer prognosis and several specific clinicopathologic characteristics compared with patients with TSCC. Conclusion: Patients with PTSCC had several unique biological tumor characteristics and a poorer prognosis than patients with TSCC. Thus, different surgical strategies should be used to treat patients with PTSCC. (C) 2017 American Association of Oral and Maxillofacial Surgeons