OBJECTIVE: To compare direct costs of treatment of children (ages 3-17) with a diagnosis of an autism spectrum disorder (autism) to a group of children having either a diagnosis of diabetes or asthma. METHODS: This was a retrospective, claims-based study of children enrolled in the California Medicaid (Medi-Cal) program from 1996-2002. Direct treatment costs were based on utilization of inpatient, outpatient, pharmacy, and ancillary services for all Medi-Cal eligible patients, starting six-months prior to a diagnosis of autism, diabetes, or asthma (index date) to 12-months following a diagnosis. Medical and prescription claims were categorized by psychiatric and non-psychiatric services. Health care costs for autistic children were then compared to costs from the randomly selected, gender matched, cohorts of children with diabetes or asthma. Descriptive statistics on demographics and non-parametric statistics on costs (Kruskal-Wallis) were performed. RESULTS: The average age of children with autism (n=731) was 8.6±4.0 years, compared with diabetes (n=731) 12.1±4.3 years, and asthma (n=731) 6.3±3.0 years. A total of 75.4% of subjects were male. Majority (37.1%) of the autism sample was White, while majority of the asthma and diabetes children were Hispanic (44.1% and 40.0%, respectively). Total median health care costs were significantly different among disease groups. Children with autism had higher annual costs (pre-diagnosis: $363; post: $1199) than children with diabetes (pre: $171; post: $649) or asthma (pre: $147; post: $424) (all P<0.0001). Psychiatric and non-psychiatric cost categories were statistically significant. Additionally, the period prevalence for autism in this population increased 114% over the study period, compared to a 42% decrease in asthma and a 3% decrease in diabetes. CONCLUSIONS: This study estimates that autistic children incur greater health care costs than children with diabetes or asthma. These findings reflect the significant cost of illness for autism relative to other chronic pediatric conditions in this Medi-Cal population.