Background No reviews have quantified the specific amounts of physical activity required for lower risks of coronary heart disease when assessing the dose-response relation. Instead, previous reviews have used qualitative estimates such as low, moderate, and high physical activity. Methods and Results We performed an aggregate data meta-analysis of epidemiological studies investigating physical activity and primary prevention of CHD. We included prospective cohort studies published in English since 1995. After reviewing 3194 abstracts, we included 33 studies. We used random-effects generalized least squares spline models for trend estimation to derive pooled dose-response estimates. Among the 33 studies, 9 allowed quantitative estimates of leisure-time physical activity. Individuals who engaged in the equivalent of 150 min/wk of moderate-intensity leisure-time physical activity (minimum amount, 2008 US federal guidelines) had a 14% lower coronary heart disease risk (relative risk, 0.86; 95% confidence interval, 0.77 to 0.96) compared with those reporting no leisure-time physical activity. Those engaging in the equivalent of 300 min/wk of moderate-intensity leisure-time physical activity (2008 US federal guidelines for additional benefits) had a 20% (relative risk, 0.80; 95% confidence interval, 0.74 to 0.88) lower risk. At higher levels of physical activity, relative risks were modestly lower. People who were physically active at levels lower than the minimum recommended amount also had significantly lower risk of coronary heart disease. There was a significant interaction by sex ( P =0.03); the association was stronger among women than men. Conclusions These findings provide quantitative data supporting US physical activity guidelines that stipulate that “some physical activity is better than none” and “additional benefits occur with more physical activity.”