Research has shown that pregnant women who smoke cigarettes increase their risk of having low birthweight (LBW) infants. Recent randomized trials indicate that women who quit smoking early in pregnancy reduce their risk of delivering a LBW infant. Using various sources, we estimated the cost-effectiveness of a smoking cessation program for preventing LBW and perinatal mortality. Assuming the program would cost $30 a participant and that 15% of the participants would quit smoking, we determined that a program offered to all pregnant smokers would shift 5,876 LBW infants to normal birthweight and would cost about $4,000 for each LBW infant prevented. Since infants born to smokers are at 20% greater risk for a perinatal death, a smoking cessation program could prevent 338 deaths at a cost of $69,542 for each perinatal death averted. Compared with the costs of caring for these LBW infants in a neonatal intensive care unit (NICU), smoking cessation programs would save $77,807,054, or $3.31 per $1 spent. The ratio of savings to costs increases to more than six to one when we include reducing long-term care for infants with disabilities secondary to LBW in the benefits from smoking cessation programs. These findings argue for routinely including smoking cessation programs in prenatal care for smokers.