The association between autism spectrum disorder (ASD) and subsequent sexually transmitted infections (STIs) and the potential effects of medications on STI risk remain unknown. In all, 5076 adolescents and young adults with ASD and 57,060 age-/sex-matched individuals without ASD were enrolled between 2001 and 2009 and followed-up to the end of 2011 for identification of subsequent STIs. The results revealed that patients with ASD were prone to acquiring an STI [hazard ratio (HR) 3.36] compared with the comparison group. Long-term use of atypical antipsychotics was associated with a lower risk of acquiring an STI later in life compared with nonuse (HR 0.34). We recommend that clinicians closely monitor risky sexual behaviors and STI risk in patients with ASD.