To determine the association between combined lifestyle factors, including healthy diet, moderate alcohol consumption, non-smoking, physical activity, and optimal weight, and cardiovascular disease (CVD) risk among younger and older adults. We conducted a literature search using PubMed, EMBASE, Cochrane Library, and EBSCO databases up to November 30, 2019 and performed dose-response analysis, subgroup analysis and meta-regression with odds ratios and 95% confidence intervals (CIs). Twenty cohort studies involving 1,090,261 participants with 46,288 cardiovascular events and mean follow-up duration of 12.33 years were included. Compared with the group with the lowest number of healthy lifestyle factors, the group with the highest number had lower CVD risk [pooled hazard ratio, 0.37 (95% CI 0.31-0.43)]. With age as an effect modifier, the lifetime risk of CVD was 0.31 (95% CI 0.24-0.41) at age 37.1-49.9 years, 0.36 (95% CI 0.30-0.45) at age 50.0-59.9 years and 0.49 (95% CI 0.38-0.63) at age 60.0-72.9 years. The hazard ratio of CVD significantly increased from 37.1 to 72.9 years of age [slope in multivariate meta-regression: 0.01 (95% CI < 0.001-0.03; p = 0.042)]. Younger adults have more cardiovascular benefits from combined healthy lifestyle factors.