Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large cohort study in Canada. The cohort consisted of the 27,318 women in the Canadian National Breast Screening Study who reported a family history of breast cancer on enrollment into the study. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000, depending upon the province. During a mean of 16.0 years of follow-up, we observed 1707 incident cases of breast cancer among women with any history of breast cancer of which 795 cases occurred among women with a mother, sister, and/or daughter with breast cancer. Among women with any family history of breast cancer, ever use of oral contraceptives was associated with a 12% reduction in risk of breast cancer (95% confidence interval [CI]=0.73-1.07), and there was an inverse trend with increasing duration of use of borderline statistical significance (p(trend)=0.03). Although we also observed a 25% lower risk of breast cancer associated with oral contraceptive use of greater than 84 months versus never use among women with a first degree relative with breast cancer, this finding was not statistically significant (95% CI=0.47-1.19, p(trend)=0.48). Our data raise the possibility that relatively long duration of oral contraceptive use may be inversely associated with risk among women with a family history of breast cancer.