This study examined psychotropic medication use among 7901 children aged 1-17 with autism spectrum disorder (ASD) in five health systems, comparing to matched cohorts with no ASD. Nearly half (48.5%) of children with ASD received psychotropics in the year observed; the most common classes were stimulants, alpha-agonists, or atomoxetine (30.2%), antipsychotics (20.5%), and antidepressants (17.8%). Psychotropic treatment was far more prevalent among children with ASD, as compared to children with no ASD (7.7% overall), even within strata defined by the presence or absence of other psychiatric diagnoses. The widespread use of psychotropics we observed, particularly given weak evidence supporting the effectiveness of these medications for most children with ASD, highlights challenges in ASD treatment and the need for greater investment in its evaluation.