Background Statins are a class of cholesterol-lowering drugs that affect many intracellular pathways that may have implications for chemoprevention against cancer. Epidemiologic data on statins and breast cancer are conflicting. We analyzed updated data from the Women’s Health Initiative (WHI) to assess the relationship between statins and breast cancer risk. Methods The population included 154,587 postmenopausal women ages 50 to 79 years, with 7,430 pathologically confirmed cases of breast cancer identified over an average of 10.8 (SD, 3.3) years. Information on statins was collected at baseline and years one, three, six, and nine. Self- and interviewer-administered questionnaires were used to collect information on risk factors. Cox proportional hazards regression was used to calculate HRs with 95% confidence intervals (CI) to evaluate the relationship between statin use and cancer risk. Statistical tests were two-sided. Results Statins were used by 11,584 (7.5%) women at baseline. The annualized rate of breast cancer was 0.42% among statin users and 0.42% among nonusers. The multivariable adjusted HR of breast cancer for users versus nonusers was 0.94 (95% CI, 0.83–1.06). In the multivariable-adjusted, time-dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71–1.07). There was no significant trend by overall duration of use (P value for trend 0.68). There was no effect of tumor stage, grade, or hormone receptor status. Conclusion Overall, statins were not associated with breast cancer risk. Impact Our study is one of the largest prospective observational studies on this topic, and substantially adds to the literature suggesting no relationship between statins and breast cancer risk.