Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children.We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children's BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children's BP.Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child's body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (β = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (β = 0.08, 95% CI 0.03 to 0.13 before conception; β = 0.07, 95%CI 0.02 to 0.12; β = 0.04, 95%CI -0.02 to 0.10; and β = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and β = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels.Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged.Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.