Key PointsQuestionIs COVID-19 booster vaccination in early pregnancy associated with an increased risk of spontaneous abortion?FindingsIn this case-control surveillance study of more than 100 000 pregnancies at 6 to 19 weeks’ gestation from 8 health systems in the Vaccine Safety Datalink, the odds of having received a COVID-19 booster vaccination in either a 28- or 42-day exposure window before spontaneous abortion were not increased compared with ongoing pregnancies.MeaningThese findings support the safety of COVID-19 booster vaccination in early pregnancy.