The authors determined the association between metabolic syndrome in early pregnancy (mean, 11.96 weeks) and the risk of preterm birth in the mother-child cohort study ("Rhea" Study) in Crete, Greece, 2007-2009. Maternal fasting serum samples were collected, and blood pressure was measured at the time of the first major ultrasound examination (n = 625). Multivariable log-binomial regression models were used. Women with metabolic syndrome were at high risk for preterm birth (relative risk (RR) = 2.93, 95% confidence interval (CI): 1.53, 5.58), with the highest risk observed for medically indicated preterm births (RR = 5.13, 95% CI: 1.97, 13.38). Among the components of metabolic syndrome, the most significant risk factor was hypertension (RR = 2.32, 95% CI: 1.28, 4.20). An elevation of 10 mm Hg in diastolic blood pressure increased the relative risk for preterm birth by 29% (RR = 1.29, 95% CI: 1.08, 1.53), while a per unit increase in the low density lipoprotein/high density lipoprotein cholesterol ratio increased this risk by 19% (RR = 1.19, 95% CI: 1.02, 1.39). Fetal weight growth restriction was associated with elevated levels of insulin (RR = 1.14, 95% CI: 1.08, 1.20) and diastolic blood pressure (RR = 1.27, 95% CI: 1.00, 1.61) in early pregnancy. These findings suggest that women with metabolic syndrome in early pregnancy had higher risk for preterm birth.