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Whether physical activity reduces the risk of postmenopausal breast cancer is uncertain; few studies have addressed this issue. We examined the association of leisure physical activity with breast cancer incidence among 37,105 postmenopausal participants in the Iowa Women’s Health Study. Women reporting the highest level of physical activity at baseline compared with women with the lowest level of activity had an age-adjusted relative risk of breast cancer of 0.92 (95% confidence interval = 0.80–1.05). Women reporting any regular leisure-time physical activity had a relative risk of 0.97 (95% confidence interval = 0.87–1.08) compared with those reporting no such regular physical activity. Adjustment for potential confounders did not appreciably alter the findings. There is little evidence from this study that physical activity later in life is associated to any appreciable extent with breast cancer incidence.