Dietary and lifestyle evolutionary discordance is hypothesised to play a role in the aetiology of CVD, including CHD and stroke. We aimed to investigate associations of a previously reported, total (dietary plus lifestyle) evolutionary-concordance (EC) pattern score with incident CVD, CHD and stroke. We used multivariable Cox proportional hazards regression to investigate associations of the EC score with CVD, CHD and stroke incidence among USA Black and White men and women ≥45 years old in the prospective REasons for Geographic and Racial Differences in Stroke study (2003–2017). The EC score comprised seven equally weighted components: a previously reported dietary EC score (using Block 98 FFQ data) and six lifestyle characteristics (alcohol intake, physical activity, sedentary behaviour, waist circumference, smoking history and social network size). A higher score indicates a more evolutionary-concordant dietary/lifestyle pattern. Of the 15 467 participants in the analytic cohort without a CVD diagnosis at baseline, 1563 were diagnosed with CVD (967 with CHD and 596 with stroke) during follow-up (median 11·0 years). Among participants in the highest relative to the lowest EC score quintile, the multivariable-adjusted hazards ratios and their 95 % CI for CVD, CHD and stroke were, respectively, 0·73 (0·62, 0·86; P trend < 0·001), 0·72 (0·59, 0·89; P trend < 0·001) and 0·76 (0·59, 0·98; P trend = 0·01). The results were similar by sex and race. Our findings support that a more evolutionary-concordant diet and lifestyle pattern may be associated with lower risk of CVD, CHD and stroke.