Background: Smoking is one of the most important modifiable risk factors for adverse maternal and neonatal outcomes. Smoking during pregnancy has been associated with fetal growth restriction, adverse pregnancy outcomes, and chronic adult diseases. Existing research has evaluated the risk of smoking on congenital defects. However, no studies have evaluated how periconception smoking affects birth defects., Objective: The purpose of this study was to assess the association of maternal smoking and the timing of periconception exposure with congenital birth defects., Study Design: This study was a population-based retrospective cohort of live births in Ohio from 2006-2015 with the use of data from birth certificates. Rates of cardiovascular, musculoskeletal, gastrointestinal, and neural tube birth defects were compared between a referent group of women who did not smoke and a group of women who smoked (1) during the preconception period of 3 months before conception only and not in the first trimester and (2) in the preconception period plus throughout the first trimester of pregnancy. Multivariate logistic regression was used to quantify the relationship between periconception smoking and the rate of birth defects after adjustment for maternal race, age, pregestational diabetes mellitus, and socioeconomic factors., Results: Of the 1,436,036 live births in the study period, 75% of mothers did not smoke during the preconception period or during pregnancy. There were 334,156 women (23.3%) who smoked during pregnancy; 6.0% of the population smoked preconception only, and 17.3% of the population smoked both during the preconception period and through the first trimester. Smoking during the preconception period only, even without first trimester exposure, was associated with a 40% increased risk of gastroschisis. Smoking that was limited to preconception only was not associated with any other individual birth defects. However, smoking through the first trimester was associated with a statistically significant increased risk of several defects that included gastroschisis and limb reduction and a composite outcome of any defect, even after adjustment for coexisting factors., Conclusion: Smoking during the period of fetal organogenesis (during the first trimester of pregnancy) is associated with increased risk of some birth defects. In this study, we provide novel data that smoking during the few months before conception, even with cessation in the first trimester, may also pose a risk for fetal malformation such as gastroschisis. These findings highlight the importance of preconception women's public health education efforts and warrant further investigation., (Copyright © 2019 Elsevier Inc. All rights reserved.)