Introduction: Women who deliver preterm births have excess risk for cardiovascular disease and diabetes later in life, perhaps related to metabolic dysregulation. Previous studies, however, have not evaluated how the pre-pregnancy metabolic status, other pregnancy characteristics and post pregnancy weight gain may be involved. Hypothesis: We hypothesized that women who delivered preterm births would have excess risk of incident metabolic syndrome (MetS) compared to women with term births independent of their pre-pregnancy metabolic profile, parity and other risk factors. Methods: We studied 1,246 women (50% Black; 624 of 1,246) in the Coronary Artery Risk Development in Young Adults (CARDIA study) who had at least one singleton birth between baseline (1985-1986) and year 25, and no MetS before pregnancy. Blood pressure, lipids, and anthropometrics were measured at baseline and at up to 7 subsequent exams. We ascertained incident MetS cases using the National Cholesterol Education Program Adult Treatment Panel III criteria and estimated the relative hazards (RH) of MetS in women with 1 or more preterm births (<37 weeks, n=306) versus 1 (n=558) and 2 or more (n=382) term births (≥37 weeks) using complementary log-log models adjusted for race, age, education, smoking, time-varying parity and pre-pregnancy metabolic syndrome components. Gestational diabetes mellitus (GDM), self-reported hypertension during pregnancy, and time dependent weight gain were considered as potential mediators. Results: Of 338 incident MetS cases in 17,212 person years, the crude incidence rate among women with preterm birth was higher than among those with 1, but not 2 or more term births (24.2, 14.4, and 32.2, respectively). After adjustment for covariates, however, including time-varying parity, the adjusted RH (95%CI) for incident MetS was 1.89 (1.24, 2.89) for women with preterm vs. term births. Additional adjustment for GDM or hypertension during pregnancy only modestly affected this estimate, but accounting for time-varying weight gain attenuated it to be non-significant (adj HR 1.42 (0.92, 2.21). Increased waist circumference (18.1 ± 12.3 vs. 15.9 ± 11.9 cm, p<0.01) and increased systolic blood pressure (13.6 ± 18.3 vs. 6.6 ± 12.5 mmHg, p<0.01) were the MetS components that changed the most from baseline to year 25 among women with preterm vs. term births. Conclusions: In conclusion, women with a history of preterm birth have an almost two-fold increased risk of incident MetS compared to those with term births after 25 years of follow up. This was independent of the pre-pregnancy metabolic status, other complications and time dependent parity. It was explained, in part, by post pregnancy weight gain.