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Trans-fatty acids (TFAs) have deleterious cardiovascular effects. Restrictions on their use were initiated in 11 New York State (NYS) counties between 2007 and 2011. The US Food and Drug Administration plans a nationwide restriction in 2018. Public health implications of TFA restrictions are not well understood.To determine whether TFA restrictions in NYS counties were associated with fewer hospital admissions for myocardial infarction (MI) and stroke compared with NYS counties without restrictions.We conducted a retrospective observational pre-post study of residents in counties with TFA restrictions vs counties without restrictions from 2002 to 2013 using NYS Department of Health’s Statewide Planning and Research Cooperative System and census population estimates. In this natural experiment, we included those residents who were hospitalized for MI or stroke. The data analysis was conducted from December 2014 through July 2016.Residing in a county where TFAs were restricted.The primary outcome was a composite of MI and stroke events based on primary discharge diagnostic codes from hospital admissions in NYS. Admission rates were calculated by year, age, sex, and county of residence. A difference-in-differences regression design was used to compare admission rates in populations with and without TFA restrictions. Restrictions were only implemented in highly urban counties, based on US Department of Agriculture Economic Research Service Urban Influence Codes. Nonrestriction counties of similar urbanicity were chosen to make a comparison population. Temporal trends and county characteristics were accounted for using fixed effects by county and year, as well as linear time trends by county. We adjusted for age, sex, and commuting between restriction and nonrestriction counties.In 2006, the year before the first restrictions were implemented, there were 8.4 million adults (53.6% female) in highly urban counties with TFA restrictions and 3.3 million adults (52.3% female) in highly urban counties without restrictions. Twenty-five counties were included in the nonrestriction population and 11 in the restriction population. Three or more years after restriction implementation, the population with TFA restrictions experienced significant additional decline beyond temporal trends in MI and stroke events combined (−6.2%; 95% CI, −9.2% to −3.2%; P < .001) and MI (−7.8%; 95% CI, −12.7% to −2.8%; P = .002) and a nonsignificant decline in stroke (−3.6%; 95% CI, −7.6% to 0.4%; P = .08) compared with the nonrestriction populations.The NYS populations with TFA restrictions experienced fewer cardiovascular events, beyond temporal trends, compared with those without restrictions.