Objectives/Hypothesis: To assess the value of both patient and tumor-related factors of oropharyngeal squamous cell carcinoma in predicting patient outcome, with respect to the three primary subsites of the disease. It was hypothesized that the subsite has a significant impact on outcome. Study Design: Historical cohort study. Methods: A chart review was conducted of 126 patients diagnosed with squamous cell carcinoma of the oropharynx over a 10-year period. The oropharynx was divided into the following subsites: 1) base of tongue, 2) tonsil and pillars, and 3) uvula, soft palate, and posterior pharyngeal wall. Patient-related factors included age and gender. Tumor-related factors included American Joint Committee on Cancer stage, T stage, N stage, and grade. These factors were compared using the end points of disease-free survival and treatment response (complete response or partial response/no response). Results: Tumor-related factors such as American Joint Committee on Cancer stage (P = .016) and T stage (P = .008) had a significant impact on treatment response. The American Joint Committee on Cancer stage (P = .030) and the T stage (P = .005) were also significant predictors of disease-free survival. Base-of-tongue lesions responded significantly worse to treatment than did tonsil and pillar or uvula, soft palate, and posterior pharyngeal wall lesions (P = .014). The disease-free survival for base-of-tongue cancer was significantly worse than for tonsil and pillar or for uvula, soft palate, and posterior pharyngeal wall cancer (P = .010). Conclusion: Patient-related factors such as age and gender were not significant in predicting disease-specific outcome. Important tumor-related factors were the American Joint Committee on Cancer stage and the T stage. Among the oropharyngeal. subsites, squamous cell carcinoma of the base of tongue was associated with the worst outcome.