© 2019 American Medical Association. All rights reserved. Importance: Administration of corticosteroids to women at high risk for delivery in the late preterm period (34-36 weeks' gestation) improves short-term neonatal outcomes. The cost implications of this intervention are not known. Objective: To compare the cost-effectiveness of treatment with antenatal corticosteroids with no treatment for women at risk for late preterm delivery. Design, Setting, and Participants: This secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter randomized clinical trial of antenatal corticosteroids vs placebo in women at risk for late preterm delivery conducted from October 30, 2010, to February 27, 2015. took a third-party payer perspective. Maternal costs were based on Medicaid rates and included those of betamethasone, as well as the outpatient visits or inpatient stay required to administer betamethasone. All direct medical costs for newborn care were included. For infants admitted to the neonatal intensive care unit, comprehensive daily costs were stratified by the acuity of respiratory illness. For infants admitted to the regular newborn nursery, nationally representative cost estimates from the literature were used. Effectiveness was measured as the proportion of infants without the primary outcome of the study: a composite of treatment in the first 72 hours of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, supplemental oxygen with a fraction of inspired oxygen of 30% or more for 4 hours or more, and extracorporeal membrane oxygenation or mechanical ventilation. This secondary analysis was initially started in June 2016 and revision of the analysis began in May 2017. Exposures: Bethamethasone treatment. Main Outcomes and Measures: Incremental cost-effectiveness ratio. Results: Costs were determined for 1426 mother-infant pairs in the betamethasone group (mean [SD] maternal age, 28.6 [6.3] years; 827 [58.0%] white) and 1395 mother-infant pairs in the placebo group (mean [SD] maternal age, 27.9 [6.2] years; 794 [56.9%] white). Treatment with betamethasone was associated with a total mean (SD) woman-infant-pair cost of $4681 ($5798), which was significantly less than the mean (SD) amount of $5379 ($8422) for women and infants in the placebo group (difference, $698; 95% CI, $186-$1257; P =.02). The Antenatal Late Preterm Steroids trial determined that betamethasone use is effective: respiratory morbidity deceased by 2.9% (95% CI, -0.5% to -5.4%). Thus, the cost-effectiveness ratio was -23 986. Inspection of the bootstrap replications confirmed that treatment was the dominant strategy in 5000 samples (98.8%). Sensitivity analyses showed that these results held under most assumptions. Conclusions and Relevance: The findings suggest that antenatal betamethasone treatment is associated with a statistically significant decrease in health care costs and with improved outcomes; thus, this treatment may be an economically desirable strategy..