Previous studies showing that Autism Spectrum Disorder (ASD) in children can have secondary effects on the child's parents are limited by small sample sizes and parent self-report. We examined the odds of depression in parents of children with ASD compared to parents of children without ASD using a large national claims database. Mothers (OR 2.95, 95% CI 2.81-3.09) and fathers (OR 2.41, 95% CI 2.25-2.58) of children with ASD were more likely to have a diagnosis of depression than parents of children without ASD. Odds of depression also increased when there was more than one child with ASD in the family and with child age. Study results reinforce the benefits of support and education for parents of children with ASD.