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Purpose: This study investigated the prevalence of Chlamydia trachomatis infection, co-infection with Human Papillomavirus (HPV) and associated risk factors in a cohort of sexually active young women enrolled in an ongoing trial on HPV vaccination at the European Institute of Oncology (IEO, Milan, Italy)., Methods: Cervical samples were collected from 591 girls (median age 18.8 years) at the beginning of their sexual activity. At the time of sample collection, 354 women had not yet been vaccinated, and 237 women had been vaccinated for at least 12 months. All samples were analyzed through a molecular assay for the detection of C. trachomatis infection. Demographic, behavioral risk factors and high-risk HPV (HR-HPV) status were investigated., Results: The prevalence of C. trachomatis infection was 4.9 % and HPV/C. trachomatis co-infection rate was 1.5 %. The exact analysis has not underlined statistical significance for the variables considered, except for the infection with HR-HPV (p < 0.001). The prevalence of C. trachomatis infection among women who had not been immunized and those already vaccinated was similar (5.6 vs 3.8 %). However, the rate of HPV/C. trachomatis co-infection was twice as high in unvaccinated women (2 %) compared to vaccinated women (0.8 %)., Conclusions: Over 16 % of young women had at least one of the two STIs investigated. The risk of C. trachomatis infection was higher in HR-HPV infected compared to HR-HPV uninfected young women. The rate of co-infection was halved in HPV-vaccinated compared to unvaccinated women. This study underlines that HPV vaccination can confer benefits also in terms of co-infections prevention, leading to a decreased risk of developing cervical malignancies.