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To access publisher's full text version of this article click on the hyperlink at the bottom of the page ; There is little evidence on the long-term association between physical activity (PA) and depressive symptoms in old age. We examined the association of midlife PA and depressive symptoms in late life. ; A large community-based population residing in Reykjavik, Iceland, participated in a longitudinal study with an average of 25 years of follow up. Midlife PA was categorized as active and inactive groups (n = 4,140, Active = 1,292, Inactive = 2,848, mean age 52±7 years). The main outcome had six or higher depressive symptoms assessed by the 15-item Geriatric Depression scale. Participants who had a history of depression (n = 226), and were diagnosed with dementia (n = 393), and had incomplete cognitive data (n = 595) and incomplete analytical data (n = 422) were excluded. Level of weekly PA was ascertained by a questionnaire at midlife. Depressive symptoms were assessed on average 25 (±4) years later. ; After controlling for demographic and health-related risk factors, those who were active at midlife were less likely to have high level of depressive symptomatology (6 or higher Geriatric Depression scale scores, odds ratio = 0.58, 95% confidence interval: 0.41-0.83, p < .005) compared with those who were inactive in midlife. After full adjustment of three domains of late-life cognitive function the results remained significant (odds ratio = 0.61, 95% confidence interval: 0.43-0.86, p = .005). ; Our study shows that midlife PA is associated with lower depressive symptoms 25 years later. Participating in regular PA in midlife may improve mental health in late life. ; National Institutes of Health/N01-AG-12100 National Institute on Aging Intramural Research Program Icelandic Heart Association Landspitali University Hospital Icelandic Parliament