The study objective was to identify demographic, medical, and health behavior factors that predict breastfeeding initiation in a rural population with low breastfeeding rates. Participants were 2323 women who experienced consecutive deliveries at 2 hospitals, with data obtained through detailed chart review. Only half the women initiated breastfeeding, which was significantly associated with higher levels of education, private insurance, nonsmoking and non-drug-using status, and primiparity, after controlling for confounders. Follow-up analyses revealed that smoking status was the strongest predictor of failure to breastfeed, with nonsmokers nearly twice as likely to breastfeed as smokers and with those who had smoked a pack per day or more the least likely to breastfeed. Findings reveal many factors placing women at risk for not breastfeeding and suggest that intervention efforts should encourage a combination of smoking cessation and breastfeeding while emphasizing that breastfeeding is not contraindicated even if the mother continues to smoke.