Birth defects now are the leading cause of infant mortality and a major contributor to heightened morbidity in the United States. Considerable medical and nonmedical resources are devoted to treating persons with birth defects. Yet, little is known about birth defects' economic burden to society and the profile of component direct and indirect costs over the lifespan of those born with specific birth defects. Using an incidence approach, we made the most comprehensive estimates to date of the cost of 18 of the most clinically significant birth defects in the United States. Our analysis provides the basis for assessing competing strategies for research and prevention.