BACKGROUND: There are limited data on the use of healthy lifestyles among adults who are candidates for primary prevention of atherosclerotic cardiovascular disease (ASCVD) with statin therapy due to a 10-year predicted risk ≥7.5%. We determined the prevalence of healthy lifestyle factors and their association with incident ASCVD and all-cause mortality in the Reason for Geographic and Racial Differences in Stroke study participants (n=5709). METHODS: Lifestyle factors (non-obese waist circumference, physical activity ≥5 times-per-week, non-smoking, low saturated-fat-intake, highest Mediterranean diet score quartile) were assessed during an in-home examination and interviewer-administered questionnaires. Adjudicated incident ASCVD (nonfatal/fatal stroke, nonfatal myocardial infarction or coronary heart disease death) and all-cause mortality were identified through active participant follow-up. RESULTS: Overall, 5.1%, 28.9%, 36.9%, 21.7% and 7.5% had 0, 1, 2, 3, and ≥4 of the 5 healthy lifestyle factors studied. There were 377 incident ASCVD events (203 CHD events and 174 strokes) and 471 deaths during 5.8 and 6.0 median years of follow-up, respectively. ASCVD incidence rates (95% CI) per 1000-person-years associated with 0, 1, 2, 3 and ≥4 healthy lifestyles were 13.4 (7.3-19.5), 12.8 (10.4-15.2), 11.0 (9.0-12.9), 11.0 (8.3-13.7), and 8.7 (4.9-12.4), respectively. Mortality rates associated with 0, 1, 2, 3 and ≥4 healthy lifestyles were 20.6 (13.3-27.8), 15.9 (13.3-18.5), 13.1 (10.9-15.2), 12.6 (9.9-15.2) and 9.2 (5.3-13.2) per 1000-person-years, respectively. The use of more healthy lifestyles was associated with lower risks for ASCVD and mortality after multivariable adjustment. CONCLUSION: Healthy lifestyles are underutilized among high-risk US adults and may substantially reduce their ASCVD risk.