Medication adherence in children is poor, particularly among those with chronic or mental health disorders. However, adherence has not been fully assessed in autism spectrum disorders (ASDs). The validated proportion of days covered method was used to quantify adherence to psychotropic medication in Medicaid-eligible children who met diagnostic criteria for ASD between 2000 and 2008 (N = 628). Among children prescribed attention deficit hyperactivity disorder (ADHD) medications, antidepressants, or antipsychotics, 44, 40 and 52 % were adherent respectively. Aggressive behaviors and abnormalities in eating, drinking, and/or sleeping, co-occurring ADHD, and the Medication Regimen Complexity Index were the most significant predictors of adherence rather than demographics or core deficits of ASD. Identifying barriers to adherence in ASD may ultimately lead to improved treatment outcomes.