Physical activity has been hypothesised to reduce endometrial cancer risk, but this relationship has been difficult to confirm because of a limited number of prospective studies. However, recent publications from five cohort studies, which together comprise 2663 out of 3463 cases in the published literature for analyses of recreational physical activity, may help resolve this question. To synthesise these new data, we conducted a meta-analysis of prospective studies published through to December 2009. We found that physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30% lower risk than inactive women. Owing to recent interest in sedentary behaviour, we further investigated sitting time in relation to endometrial cancer risk using data from the NIH-AARP Diet and Health Study. We found that, independent of the level of moderate-vigorous physical activity, greater sitting time was associated with increased endometrial cancer risk. Thus, limiting time in sedentary behaviours may complement increasing level of moderate-vigorous physical activity as a means of reducing endometrial cancer risk. Taken together with the established biological plausibility of this relation, the totality of evidence now convincingly indicates that physical activity prevents or reduces risk of endometrial cancer.