The purpose of this study was to determine the relationships among preconception stressful life events (PSLEs), women's alcohol and tobacco use before and during pregnancy, and infant birthweight. Data were from the Early Childhood Longitudinal Study-Birth Cohort (n = 9,350). Data were collected in 2001. Exposure to PSLEs was defined by indications of death of a parent, spouse, or previous live born child; divorce or marital separation; or fertility problems prior to conception. Survey data determined alcohol and tobacco usage during the 3 months prior to and in the final 3 months of pregnancy. We used staged multivariable logistic regression to estimate the effects of women's substance use and PSLEs on the risk of having a very low (<1,500 g, VLBW) or low (1,500-2,499 g, LBW) birthweight infant, adjusting for confounders. Women who experienced any PSLE were more likely to give birth to VLBW infants (adjusted odds ratio [AOR] = 1.35; 95 % confidence interval [CI] = 1.10-1.66) than women who did not experience any PSLE. Compared to women who never smoked, women who smoked prior to conception (AOR = 1.31; 95 % CI = 1.04-1.66) or during their last trimester (AOR = 1.98; 95 % CI = 1.56-2.52) were more likely to give birth to LBW infants. PSLEs and women's tobacco use before and during pregnancy are independent risk factors for having a lower birthweight baby. Interventions to improve birth outcomes may need to address women's health and health behaviors in the preconception period.