Gender of a fetus is associated with maternal hormonal milieu and may therefore modify maternal risk of ovarian cancer following a birth. We evaluated the relation between gender of offspring and maternal risk of epithelial ovarian cancer in a large case-control study nested within a nationwide cohort. Cohort members were identified in the Swedish Fertility Register. Cases of invasive epithelial ovarian cancer were identified in the Swedish National Cancer Register from 1961 to 2001. Five controls were matched by age to each case. A total of 7,407 cases and 37,658 controls with only singleton births were included in the analysis. We fit logistic regression models to study the association between gender of offspring and ovarian cancer risk, controlling for covariates. Maternal risk of ovarian cancer was reduced with increasing numbers of male offspring and increased with number of female offspring. Compared with women who gave birth to only girls, multivariate odds ratios (95% confidence interval) of invasive epithelial ovarian cancer were 0.92 (0.87-0.98) for those who gave birth to one boy, 0.87 (0.80-0.94) for two boys, and 0.82 (0.73-0.94) for three or more boys (P value test for trend <0.001). There was a positive but nonsignificant association with number of girls. Similar results were observed when restricting the analysis to women born before 1935. Our findings suggest that hormonal and physiologic conditions in pregnancy with male, but not with female, offspring are associated with a lowered maternal risk of invasive epithelial ovarian cancer.