This study aimed to determine the association of AGT1R and AGT2R polymorphisms with preeclampsia and whether these are affected by environmental factors and fetal sex. Overall 3234 healthy nulliparous women, their partners and babies were recruited prospectively to the SCOPE study in Adelaide and Auckland. Data analyses were confined to 2121 Caucasian parent-infant trios, among which 123 had preeclamptic pregnancies. 1185 uncomplicated pregnancies served as controls. DNA was extracted from buffy coats and genotyped by utilizing the Sequenom MassARRAY system. Doppler sonography on the uterine arteries was performed at 20 weeks’ gestation. When the cohort was stratified by maternal BMI, in women with BMI≥25kg/m2, the AGT2R C4599A AA genotype in mothers and neonates was associated with an increased risk for preeclampsia compared with the CC genotype [OR 2.1 (95% CI 1.0-4.2) and OR 3.0 (95% CI 1.4-6.5), respectively]. In the same subset of women, paternal AGT2R C4599A A allele was associated with an increased risk for preeclampsia and uterine artery bilateral notching at 20 weeks’ gestation compared with the C allele [OR 1.9 (95% CI 1.1-3.2) and OR 2.1 (95% CI 1.3-3.4), respectively]. AGT2R C4599A in mothers, fathers and babies was associated with preeclampsia and this association was only apparent in pregnancies in which the women had a BMI≥25kg/m2, suggesting a gene-environment interaction.