Depressive disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous papers in the literature investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial.We explored the relationship between depressive disorder and the subsequent development of STIs including human immunodeficiency virus (HIV) infection, primary, secondary, and latent syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis.We identified patients who were diagnosed with the depressive disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without the depressive disorder who were matched according to age and sex. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.The depression cohort consisted of 5959 patients, and the comparison cohort consisted of 23,836 matched control patients without depressive disorder. The incidence of subsequent STIs (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.34-1.76) was higher among the depressed patients than among the patients in the comparison cohort. Furthermore, female gender compared to male (HR 1.58, 95% CI 1.24-2.01) and young age <40-year-old (HR 1.79, 95% CI 1.38-2.32) are both risk factors for acquisition of STIs in depression patient. For individual STI, the results indicated that the patients with depressive disorder exhibited a markedly higher risk for subsequent STIs including HIV infection, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis.Depressive disorder might increase the risk of subsequent newly diagnosed STIs including HIV infection, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis in Taiwan population. Clinicians should pay particular attention to STIs in depression patients. Depression patients, especially those with the history of high-risk sexual behaviors, should be routinely screened for STIs.