Objectives: To examine whether moderate to vigorous physical activity (MVPA) measured using accelerometry is associated with incident falls and whether associations differ according to physical function or history of falls. Design: Prospective study with baseline data collection from 2012 to 2014 and 1 year of follow-up. Setting: Women's Health Initiative participants living in the United States. Participants: Ambulatory women aged 63 to 99 (N = 5,545). Measurements: Minutes of MVPA per day measured using an accelerometer, functional status measured using the Short Physical Performance Battery (SPPB), fall risk factors assessed using a questionnaire, fall injuries assessed in a telephone interview, incident falls ascertained from fall calendars. Results: Incident rate ratios (IRRs) revealed greater fall risk in women in the lowest quartile of MVPA compared to those in the highest (IRR = 1.18, 95% confidence interval = 1.01–1.38), adjusted for age, race and ethnicity, and fall risk factors. Fall rates were not significantly associated with MVPA in women with high SPPB scores (9–12) or one or fewer falls in the previous year, but in women with low SPPB scores (≤ 8) or a history of frequent falls, fall rates were higher in women with lower MVPA levels than in those with higher levels (interaction P <.03 and <.001, respectively). Falls in women with MVPA above the median were less likely to involve injuries requiring medical treatment (9.9%) than falls in women with lower MVPA levels (13.0%) (P <.001). Conclusion: These findings indicate that falls are not more common or injurious in older women who engage in higher levels of MVPA. These findings support encouraging women to engage in the amounts and types of MVPA that they prefer. Older women with low physical function or frequent falls with low levels of MVPA are a high-risk group for whom vigilance about falls prevention is warranted.