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Smoke-free legislation has been associated with lower rates of cardiovascular disease hospital admissions in ecological studies. However, prior studies lacked detailed information on individual-level factors (eg, sociodemographic and clinical characteristics) that could potentially confound associations. Our objective was to estimate associations of smoke-free policies with incident cardiovascular disease in a longitudinal cohort after controlling for sociodemographics, cardiovascular disease risk factors, and policy covariates.Longitudinal data from 3783 black and white adults in the CARDIA study (Coronary Artery Risk Development in Young Adults; 1995–2015) were linked to state, county, and local 100% smoke-free policies in bars, restaurants, and nonhospitality workplaces by Census tract. Extended Cox regression estimated hazard ratios (HRs) of incident cardiovascular disease associated with time-dependent smoke-free policy exposures. Models were adjusted for sociodemographic characteristics, cardiovascular disease risk factors, state cigarette tax, participant-reported presence of a smoking ban at their workplace, field center, and metropolitan statistical area poverty.During a median follow-up of 20 years (68 332 total person-years), 172 participants had an incident cardiovascular disease event (2.5 per 1000 person-years). Over the follow-up period, 80% of participants lived in areas with smoke-free policies in restaurants, 67% in bars, and 65% in nonhospitality workplaces. In fully adjusted models, participants living in an area with a restaurant, bar, or workplace smoke-free policy had a lower risk of incident cardiovascular disease compared with those in areas without smoke-free policies (HR, 0.75, 95% confidence interval, 0.49–1.15; HR, 0.76, 95% confidence interval, 0.47–1.24; HR, 0.54, 95% confidence interval, 0.34–0.86, respectively; HR, 0.58, 95% confidence interval, 0.33–1.00 for living in an area with all 3 types of policies compared with none). The estimated preventive fraction was 25% for restaurant policies, 24% for bar policies, and 46% for workplace policies.Consistent with prior ecological studies, these individual-based data add to the evidence that 100% smoke-free policies are associated with lower risk of cardiovascular disease among middle-aged adults.