Introduction The nature of the relationship between maternal tobacco smoking during pregnancy and the occurrence of children's behavioral problems is still a matter of controversy. We tested this association using data collected among a sample of pregnant women and their offspring followed up from birth to early adolescence (age 12 years), accounting for multiple parent, child, and family characteristics. Aims and Methods Data come from 1424 mother-child pairs participating in the etude des Determinants pre et post-natals precoces du developpement psychomoteur et de la sante de l'ENfant mother-child cohort in France. Using repeated measures (3, 5.5, 8, and 11.5 years) of the mother-reported Strengths and Difficulties Questionnaire, we estimated trajectories of children's emotional and behavioral difficulties. Two aspects of maternal smoking were studied: The timing (nonsmoker, smoking during the periconceptional period, or throughout pregnancy) and the level of use (cigarettes/day) during the first trimester of pregnancy. Robust Poisson regression models controlled for confounding factors including maternal mental health and socioeconomic characteristics using propensity scores with the overlap weighting technique. Results Contrary to bivariate analyses, in propensity score-controlled regression models, maternal smoking throughout pregnancy was no longer significantly associated with offspring emotional or behavioral difficulties. Maternal heavy smoking (>= 10 cigarettes/day) remained significantly associated with intermediate levels of conduct problems (RR 1.25, 95% CI 1.19 to 1.31). Conclusions The association between maternal smoking in pregnancy and offspring's emotional and behavioral difficulties appears to be largely explained by women's other characteristics. However, maternal heavy smoking appears to be related to offspring behavioral difficulties beyond the role of confounding characteristics. Implications The relationship between maternal smoking during pregnancy (in two modalities: Timing and level of smoking) and behavioral difficulties in children is still a matter of debate. While the relationship between any maternal tobacco use and offspring behavioral difficulties appears to be largely explained by confounding factors, heavy maternal smoking in the first trimester of pregnancy seems to be associated with offspring behavioral difficulties beyond the socioeconomic and mental health characteristics transmitted across generations.