We assessed the relationship of lactation to long-term maternal weight gain among African-American women, who have a lower prevalence of lactation and a higher prevalence of obesity than other US women. A pregnancy cohort of 3,147 African-American women from the Black Women's Health Study who gave birth for the first time between 1995 and 2003 was followed for 8 years postpartum. Participants provided data on weight, lactation, gestational weight gain, education, diet, and exercise. Mean differences in weight gain were estimated in multivariable models. Overall, lactation was not associated with mean weight gain. However, the association was modified by prepregnancy body mass index (BMI; weight (kg)/height (m)2) (P for interaction = 0.03): Among women with BMI <30 prior to the pregnancy, mean weight gain decreased with increasing months of lactation (P for trend < 0.01), whereas among obese women (BMI ≥30), mean weight gain increased with increasing duration of lactation (P for trend = 0.04). Adjusted mean differences for ≥12 months of lactation relative to no lactation were −1.56 kg (95% confidence interval: −2.50, −0.61) among nonobese women and 2.33 kg (95% confidence interval: −0.35, 5.01) among obese women. The differences in postpartum mean weight gain persisted over the 8-year study period. Residual confounding by factors more common in women who breastfeed longer may have influenced the results.