The cost of ASD in the U.S. is estimated using a forecast model that for the first time accounts for the true historical increase in ASD. Model inputs include ASD prevalence, census population projections, six cost categories, ten age brackets, inflation projections, and three future prevalence scenarios. Future ASD costs increase dramatically: total base-case costs of $223 (175-271) billion/year are estimated in 2020; $589 billion/year in 2030, $1.36 trillion/year in 2040, and $5.54 (4.29-6.78) trillion/year by 2060, with substantial potential savings through ASD prevention. Rising prevalence, the shift from child to adult-dominated costs, the transfer of costs from parents onto government, and the soaring total costs raise pressing policy questions and demand an urgent focus on prevention strategies.