Substance use in pregnancy is associated with severe maternal and fetal morbidities and substantial economic costs. Our study evaluated the economic impact of a behavioral intervention that integrated motivational enhancement therapy with cognitive behavioral therapy (MET-CBT) for treatment of substance use in pregnancy, in comparison with brief advice. In a randomized controlled trial, we found that a novel behavioral intervention integrating motivational enhancement therapy with cognitive behavioral therapy had similar effect on substance use and birth outcomes and the overall cost of care was similar between the two groups, and was primarily influenced by labor and delivery cost.  MET-CBT did not reduce overall medical costs up to 3-months postpartum.