Importance: Knowledge of the risk factors for oropharyngeal hemorrhage after chemoradiation therapy will guide clinicians in monitoring high-risk patients in order to prevent a life-threatening complication. Objective: To determine risk factors for the development of oropharyngeal hemorrhage following chemoradiation therapy without surgery for oropharyngeal squamous cell carcinoma. Design: Retrospective review of medical records of patients treated during the period January 2005 through December 2010. Setting: University of Louisville Hospital. Participants: The study population comprised 139 patients with a diagnosis of oropharyngeal squamous cell carcinoma who were treated with chemoradiation therapy without surgery. All patients received primary treatment from our institution. Those with recurrent tumors or prior oropharyngeal resections, with the exception of tonsillectomy, were excluded from the study. Patients were divided into 2 groups: those who did not hemorrhage following treatment (n = 129) and those who developed oropharyngeal hemorrhage (n = 10), defined as hemorrhage necessitating procedural intervention. Main Outcomes and Measures: Four clinical variables were measured: T category, radiation therapy method, weight loss, and age. Results: Results from logistic regression analysis showed that significant risk factors for hemorrhage were advanced T category (odds ratio [OR], 8.40 [95% CI, 2.44-46.61]; P < .001), radiation therapy method (OR, 79.94 [95% CI, 2.64-<999.90]; P = .008), weight loss (OR, 0.89 [95% CI, 0.79-0.98]; P = .01), and increased age (OR, 0.93 [95% CI, 0.86-0.99]; P = .03). After multiple logistic regression analyses, only advanced T category remained statistically significant (adjusted OR, 6.6 [95% CI, 1.2-infinity]; P = .02). Results from Kaplan-Meier survival analysis on all patients showed that those who hemorrhaged had significantly shorter survival time than those who did not (P = .04). However, after multivariate analysis with a Cox proportional hazards regression model, hemorrhage no longer remained a significant factor (P = .13). Conclusions: For patients with oropharyngeal squamous cell carcinoma treated with chemoradiation without surgery, advanced T category is the most important determinant of developing oropharyngeal hemorrhage; furthermore, hemorrhage occurs in the presence of either recurrent and/or persistent disease or radiation necrosis. Survival analysis indicates that development of hemorrhage is a poor prognostic marker for overall survival.