To estimate excess direct medical costs of low birth weight from maternal smoking and short-term cost savings from smoking cessation programs before or during the first trimester of pregnancy. Simulations using data on neonatal costs per live birth. Outcome measures are mean US excess direct medical cost per live birth, total excess direct medical cost, reductions in low birth weight, and savings in medical costs from an annual 1 percentage point drop in smoking prevalence among pregnant women. Mean average excess direct medical cost per live birth for each pregnant smoker (in 1995 dollars) was $511; total cost was $263 million. An annual drop of 1 percentage point in smoking prevalence would prevent 1300 low birth weight live births and save $21 million in direct medical costs in the first year of the program; it would prevent 57,200 low birth weight infants and save $572 million in direct medical costs in 7 years. Smoking cessation before the end of the first trimester produces significant cost savings from the prevention of low birth weight.