Objective: The objective of this study was to perform a cost-benefit analysis of routine second-trimester screening ultrasonography in the United States as compared with performing ultrasonography only in the presence of indications. Study Design: It was assumed that 1 million pregnant women are available annually who otherwise would not have an indication for an ultrasonographic examination. Cost savings from early detection and therapeutic abortion were considered only for fetal conditions for which lifetime cost estimates are available, including spina bifida, major cardiac disease, cleft lip or palate, renal agenesis or dysgenesis, urinary obstruction, lower or upper limb reduction, omphalocele, gastroschisis, and diaphragmatic hernia. Two separate cost-benefit analyses were considered with the range of fetal anomaly detection rates before 24 weeks’ gestation as reported by tertiary and non-tertiary centers in the Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial. Potential cost savings from averting treatment for preterm labor and postdate gestations were also considered. Results: The ratio of savings to cost was between 1.35 and 1.70 (savings of $1.35-$1.70 per $1 spent) if the ultrasonographic examinations were performed in tertiary care centers. The ratio of savings to cost was between 0.40 and 0.74 (loss of $0.26-$0.60 per $1 spent) if the examinations were performed in nontertiary centers. If the screening ultrasonography was performed in tertiary centers, the expected annual net benefits were estimated at $97 to 189 million. If ultrasonographic screening was performed in nontertiary centers, the expected annual net losses were estimated at $69 to 161 million. Conclusion: Routine second-trimester ultrasonographic screening appears to be associated with net benefits only if the ultrasonography is performed in tertiary care centers. (Am J Obstet Gynecol 2000; 182:655-60.)