This retrospective database study of 44,862 patients who had a history of a primary head and neck malignancy was conducted to identify any clinical variables that may predict the occurrence of a second primary head and neck malignancy. During a mean follow-up of 42.2 months, a second head and neck primary developed in 941 of these patients (2.1%). Statistical analyses revealed that a higher incidence of a second primary was associated with increased age and a location of the first primary in the larynx/hypopharynx, the oropharynx, a major salivary gland, or the nasopharynx. A lower incidence was associated with the presence of cervical nodal disease or treatment of the first primary with radiation therapy. Factors that had no effect on the risk of a second primary included sex, the size of the first primary tumor, a first-primary site in the oral cavity, and treatment of the first primary with cancer-directed surgery. The risk of a second primary head and neck cancer remained constant for at least 10 years.