This study examined the effects of substance use (alcohol, tobacco and/or drugs (cocaine and/or marijuana)) and healthy maternal behavior (prenatal care, prenatal class, vitamins, regular exercise) during gestation on pregnancy outcome. Live births from the nationally representative 1988 National Maternal and Infant Health Survey were analyzed. Pregnancy outcomes (infant birth weight, weeks gestation, one and five minute Apgar scores, whether or not the infant was transferred to another hospital after delivery and whether or not the infant was rehospitalized) were studied in multiple linear regression and logistic regression models. The relationship of the interaction of substance use and healthy behaviors and outcome was studied in all models. It was found that women engaging in substance use while pregnant were less likely to engage in healthy behavior. However, in general, engaging in healthy behaviors had the largest positive effects on outcome for those women who engaged in multiple substance use while pregnant. Significant interactions between healthy and unhealthy behavior were found for birth weight, weeks gestation and five minute Apgar scores, indicating that engaging in positive health behavior may help moderate some of the deleterious consequences of substance use during pregnancy.