Children with autism spectrum disorder (ASD) have a variety of medical and psychiatric conditions and an increased use of health care services. There is limited information about the prevalence of psychiatric and medical conditions in adolescents and young adults with ASD. Our objective was to describe the frequency of medical and psychiatric conditions in a large population of diverse, insured transition-aged individuals with ASD. Participants included Kaiser Permanente Northern California members who were enrolled from 2013 to 2015 and who were 14 to 25 years old. Individuals with ASD (n = 4123) were compared with peers with attention-deficit/hyperactivity disorder (n = 20 615), diabetes mellitus (n = 2156), and typical controls with neither condition (n = 20 615). Over one-third (34%) of individuals with ASD had a co-occurring psychiatric condition; the most commonly reported medical conditions included infections (42%), obesity (25%), neurologic conditions (18%), allergy and/or immunologic conditions (16%), musculoskeletal conditions (15%), and gastrointestinal (11%) conditions. After controlling for sex, age, race, and duration of Kaiser Permanente Northern California membership, most psychiatric conditions were significantly more common in the ASD group than in each comparison group, and most medical conditions were significantly more common in the ASD group than in the attention-deficit/hyperactivity disorder and typical control groups but were similar to or significantly less common than the diabetes mellitus group. Although more research is needed to identify factors contributing to this excess burden of disease, there is a pressing need for all clinicians to approach ASD as a chronic health condition requiring regular follow-up and routine screening and treatment of medical and psychiatric issues.