Key PointsQuestionIs the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, associated with preterm birth (PTB)?FindingsIn this cohort study using 2018 national birth certificate data for 3 659 099 births, PTB rates were significantly lower among individuals with very low MVI compared with those with very high MVI (7% vs 10%). The association between very high MVI and PTB remained after adjustment for patient characteristics.MeaningThe findings of this study suggest that the MVI is a useful measure for county-level PTB risk and may provide guidance for communities working to improve perinatal health.