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The purpose of the current study was to analyze the current patterns in pharmacotherapy and polypharmacy for youth with autism spectrum disorders (ASD) relative to the patterns among students with other neurodevelopmental disabilities or emotional disabilities (ONDED). We used data from the National Longitudinal Transition Study 2 to calculate descriptive statistics and risk ratios. The results indicate that youths with ASD were more likely to use medications than the ONDED group. Overall, the risk was higher when the youths were younger, especially for antipsychotics and antidepressants. Furthermore, students with ASD aged 13 to 16 were five times more likely to take more than three medications concurrently compared the ONDED group. The disparity between the two groups reduced over eight years.