IMPORTANCE: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalizations. In August 2023, the US Food and Drug Administration approved a bivalent RSV prefusion F subunit-based vaccine (RSVpreF) for maternal immunization to protect newborns. Sequential surveillance analysis provides information on the safety of a vaccine during its initial uptake. OBJECTIVE: To report the sequential surveillance findings for 10 prespecified safety outcomes of exposure to RSVpreF during pregnancy over the course of its first vaccination season in the US. DESIGN, SETTING, AND PARTICIPANTS: This cohort study with a sequential surveillance design used health plan data from 5 research partners. Health insurance data were analyzed across 5 sequential surveillance periods from April 25, 2024, through April 10, 2025. Pregnancies of individuals aged 15 to 54 years that culminated in a live birth or stillbirth and reached 32 gestational weeks were included. Cohorts included pregnancies exposed to RSVpreF (between September 22, 2023, and August 9, 2024); comparator pregnancies receiving influenza, COVID-19, and/or Tdap (tetanus, diphtheria, and acellular pertussis) vaccines but not the RSVpreF concurrently; and historical comparator pregnancies (vaccinated between September 1, 2018, and January 31, 2023). EXPOSURE: RSVpreF or comparator vaccines (influenza, COVID-19, and/or Tdap but not RSVpreF) between 32 through 36 weeks' gestation. MAIN OUTCOMES AND MEASURES: Primary outcomes were preterm birth and pregnancy-associated hypertensive disorders (composite of gestational hypertension; preeclampsia; eclampsia; hemolysis, elevated liver enzymes, and low platelet syndrome; or preexisting hypertension superimposed with preeclampsia or eclampsia). Secondary outcomes included premature rupture of membranes (PROM), preterm labor without preterm delivery, preterm PROM, maternal Guillan-Barré syndrome, and stillbirth. Infant outcomes were large for gestational age, small for gestational age, and low birth weight. Crude incidence proportions (IPs) and adjusted relative risks (ARR) were identified for these outcomes. RESULTS: Among the 13 619 RSVpreF-exposed pregnancies included in the analysis, the mean (SD) maternal age was 33.3 [4.6] years. The most common safety outcomes were pregnancy-associated hypertensive disorders (IP, 17.3%; 95% CI, 16.6%-17.9%) and PROM (IP, 14.1%; 95% CI, 13.5%-14.7%). Risk of preterm birth was not elevated compared with the concurrent comparator (ARR, 0.79; 95% CI, 0.65-0.98) or historical comparator (ARR, 0.87; 95% CI, 0.78-0.96). Beginning with the second surveillance period, statistically significantly elevated risks were detected for pregnancy-associated hypertensive disorders (concurrent comparator: ARR, 1.14 [95% CI, 1.02-1.27]; historical comparator: ARR, 1.29 [95% CI, 1.24-1.34]), PROM (concurrent comparator: ARR, 1.09 [95% CI, 0.97-1.22]; historical comparator: ARR, 1.14 [95% CI, 1.09-1.19]), and preterm PROM (historical comparator: ARR, 1.18; 95% CI, 1.08-1.29). No other increased risks were observed. CONCLUSIONS AND RELEVANCE: In this study using a sequential surveillance design, there was no association between RSVpreF vaccination during pregnancy and preterm birth; however, potential increased risks of pregnancy-associated hypertensive disorders, PROM, and preterm PROM could not be ruled out, due to limited confounding control available in the early postlicensure period. Further epidemiological studies are needed to refine risk estimates and account for other confounding factors.