Lung cancer survivors are at risk of developing second primary cancers (SPCs). Although some risk factors for the development of SPCs have been addressed, their impacts have not been clarified. This study, based on Taiwan’s National Health Insurance Research Database (NHIRD), a nationwide database, was designed to investigate the risk factors for SPCs in patients with initial lung cancer and identify the impacts of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment on the development of SPCs. In this study, 37,954 individuals were included, of whom 2819 had SPCs. These patients were further divided into the second primary lung cancers (SPLC) and second primary extrapulmonary cancer (SPEC) groups. Among the patients with lung cancer without SPCs, those aged