In the present study we explore the association between the ponderal index (PI) at birth and the metabolic syndrome (MetS) in middle-aged population in China. A total of 975 men and women aged 41-52 years with detailed birth records were followed up and recruited for clinic examinations, involving anthropometry and measurements of blood pressure, fasting plasma glucose, serum lipid profile. The MetS was diagnosed according to the National Cholesterol Education Program (Adult Treatment Panel III) definition. Multivariate logistic regression analysis estimated the effect of PI on MetS and the interaction between PI at birth and adult body mass index (BMI). The average prevalence of MetS was 19.3%, with rates of 23.7%, 22.9%, 16.9% and 16.5% in those who at birth were <25th percentile, the 25th-50th percentile, the 50th-75th percentile and >75th percentile PI respectively, with a significant decreasing trend (x(2) (for trend) = 5.661, P = 0.017). Logistic regression analysis showed that 25.7% of the occurrence of MetS was attributable to PI at birth and adult BMI both acting independently and synergistically. In summary thinness at birth predicts the later occurrence of MetS, as well as modifying the association between later BMI and MetS. Overweight later in life was most deleterious for those with growth retardation at birth.