The links between preterm birth, low birth weight, and adult vascular/metabolic morbidity remain unclear. Genetic susceptibility of babies related to these three conditions might contribute to this long-term association. We tested whether the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene could play a role in birth weight and duration of gestation. We genotyped two independent cross-sectional studies from Northern Ireland (n = 382 and 620). In combined populations, the PPARG Ala12 allele was associated (P = 0.03) with lower birth weight, primarily caused by shorter gestational duration (P = 0.04). The frequency of Ala12 allele carriers was higher (P = 0.027) in the group of individuals born before term (35%, n = 60) than in the group of individuals born at term (22%, n = 942). The odds ratios (95% CI) of preterm birth for Ala12 allele carriers were 1.9 (1.1-3.4), P = 0.022, and 4.2 (1.9-9.7), P = 0.0006 (adjusted for sex, maternal age, and study), when considering 37 or 35 weeks of pregnancy as a threshold for preterm birth, respectively. Interestingly, the same allele was also associated with a moderate decreased risk of miscarriages in mothers. In conclusion, the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life.