OBJECTIVE: To provide U.S. case-based preeclampsia health care cost estimates for mothers and infants from a U.S. payer perspective, with comparisons with both uncomplicated and hypertensive pregnancies. METHODS: Electronic health record and billing data from a large regional integrated health care system in Pennsylvania were used to identify mother-singleton infant pairs with deliveries between 2010 and 2015. Data on clinical care and costs using actual payment amounts were compiled from 20 weeks of gestation to 6 weeks postdelivery for mothers and birth to 12 months for infants. Three defined pregnancy study cohorts, uncomplicated, hypertension and preeclampsia, were matched using a 1:1:1 ratio on the basis of maternal age, parity, body mass index, and comorbidities. Costs per pregnancy were calculated in 2015 dollars and preeclampsia incremental costs estimated by subtracting the average cost of the matched cohorts. RESULTS: The final study population included 712 matched mother-infant pairs in each cohort. The mean combined maternal and infant medical care costs in the preeclampsia cohort of $41,790 were significantly higher than those for the uncomplicated cohort of $13,187 (P<.001) and hypertension cohort of $24,182 (P<.001), and were largely driven by differences in the infant costs. The mean infant cost in the preeclampsia cohort were $28,898, in the uncomplicated cohort $3,669 and $12,648 in the hypertension cohort (P<.001). Mothers with preeclampsia delivered 3 weeks earlier (median 36.5 weeks of gestation) than women in the uncomplicated cohort and more than 2 weeks earlier than women in the hypertension cohort. A significantly larger percentage of women with preeclampsia and their infants experienced adverse events (13.9% for mothers and 14.6% for infants) compared with unaffected women (4.1% and 0.7%) and those with hypertension (9.4% and 4.8%), respectively (P<.001). CONCLUSION: The economic burden of preeclampsia health care is significant with the main cost drivers being infant health care costs associated with lower gestational age at birth and greater adverse outcomes. FUNDING SOURCE: This study is funded by Progenity, Inc.