Radiation with or without chemotherapy is considered the mainstay of treatment for the majority of patients with oropharyngeal cancer. The goal of this study was to analyze competing causes of mortality in patients with oropharyngeal cancer with long-term follow-up. We queried the Surveillance, Epidemiology and End Results (SEER) database and identified 3728 patients with oropharyngeal cancer treated between 1988 and 2001 with definitive radiotherapy. We analyzed predictors of overall survival and risks of mortality from index oropharyngeal cancer, second primary cancer, cardiovascular disease and other causes using a cumulative incidence analysis and Cox multivariate analysis. With a median follow-up of 6.8 years, the 5- and 10-year overall survival was 37 and 22%, respectively. At 5 years, the risk of mortality from primary oropharyngeal cancer was 35%. Between years 3 and 10, 69% of mortalities were attributed to causes other than the index cancer. Despite advances in the non-surgical treatment of oropharyngeal cancer, patients remain at significant risk of cancer- and non-cancer-related mortality.