Breastfeeding is a protective factor for women and children. Women who smoke cigarettes during pregnancy are less likely to initiate or persist in breastfeeding. However, less is known about why this is the case. The present study ( = 247) prospectively examined maternal/child factors that influence breastfeeding in a low-income, racially diverse at-risk sample of smoking and nonsmoking women. Pregnant women were recruited at their first prenatal appointment in an urban hospital and followed through 24-month postnatally. Women reported on the average number of cigarettes smoked/day during pregnancy, psychopathology, breastfeeding behavior, and infant reactivity. Although a greater number of cigarettes smoked/day during pregnancy was associated with a lower likelihood of initiating or persisting in breastfeeding, maternal age, education, and infant reactivity offered predictive utility above and beyond maternal smoking. Smokers were less likely to initiate breastfeeding and breastfed for shorter duration than demographically similar nonsmokers; however, one of the mechanisms for reduced breastfeeding may be the psychosocial factors of younger age and lower education. Further, infant reactivity was also found to reduce the likelihood of initiating and persisting with breastfeeding.