Background: The aim of this study was to identify risk factors for the development of second primary tumors (SPTs) in the head and neck region, lungs, and esophagus in patients with head and neck cancer. Methods: We collected data from 1581 patients. A cause-specific Cox model for the development of an SPT was fitted, accounting for the competing risks residual/recurrent tumor and mortality. Results: Of all patients, 246 (15.6%) developed SPTs. Analysis showed that tobacco and alcohol use, comorbidity, and the oral cavity subsite were risk factors for SPTs. The C-index, the discriminative accuracy, of the model for SPT was 0.65 (95% confidence interval, 0.61–0.68). Conclusions: Our results show that there is potential to identify patients who have an increased risk to develop an SPT. This might increase their survival chances and quality of life. More research is needed to provide head and neck clinicians with definitive recommendations.