Previous studies have observed an association between ABO blood group and risk of certain malignancies, including ovarian cancer; however, no prospective studies of the association with ovarian cancer risk are available. Using data from 49,153 women in the Nurses' Health Study, we examined the association between ABO blood group and incidence of epithelial ovarian cancer. Study participants reported their blood type and Rh factor in 1996, and 234 women were diagnosed with incident ovarian cancer during 10 years of follow-up. We used Cox proportional hazards regression to model the incidence rate ratios (RR) and 95% confidence intervals (CI) of ovarian cancer for each blood group category. Compared to women with blood group O, women with blood group AB or B had a nonsignificant 38% increase in ovarian cancer incidence (95% CI = 0.88-2.16 for blood group AB and 0.96-1.99 for blood group B), whereas blood group A was not associated with risk (RR = 0.95, 95% CI = 0.70-1.30). Combining blood groups AB and B, we observed a statistically significant positive association with presence versus absence of the B antigen overall (RR = 1.41, 95% CI = 1.06-1.88) and for the serous invasive subtype (RR = 1.53, 95% CI = 1.08-2.17). In this large, prospective cohort of women, presence of the B antigen was positively associated with ovarian cancer incidence, whereas blood group A was not associated with risk. Additional studies are needed to confirm this association and to explore the mechanisms through which blood group may influence ovarian cancer risk.