The American Academy of Pediatrics recommends universal screening for autism spectrum disorder at 18 and 24 months. This study compared the cost-effectiveness of universal or high-risk screening to surveillance monitoring. Simulation models estimated the costs and outcomes from birth to age 6 years. The incremental cost per child diagnosed by 36 months was $41,651.6 for high-risk screening and $757,116.9 for universal screening from the societal perspective. Universal screening may not be a cost-effective approach to increase earlier treatment initiation, as most children initiated treatment after age 60 months. Eliminating wait times resulted in more children initiated treatment by 48 months, but at a high initial cost that may be offset by future cost-savings related to better outcomes.