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Although several studies have examined associations between temperature and cardiovascular-disease-related mortality, fewer have investigated the association between temperature and the development of acute myocardial infarction (MI). Moreover, little is known about who is most susceptible to the effects of temperature.We analyzed data from the Worcester Heart Attack Study, a community-wide investigation of acute MI in residents of the Worcester (MA) metropolitan area. We used a case-crossover approach to examine the association of apparent temperature with acute MI occurrence and with all-cause in-hospital and postdischarge mortality. We examined effect modification by sociodemographic characteristics, medical history, clinical complications, and physical environment.A decrease in an interquartile range in apparent temperature was associated with an increased risk of acute MI on the same day (hazard ratio = 1.15 [95% confidence interval = 1.01–1.31]). Extreme cold during the 2 days prior was associated with an increased risk of acute MI (1.36 [1.07–1.74]). Extreme heat during the 2 days prior was also associated with an increased risk of mortality (1.44 [1.06–1.96]). Persons living in areas with greater poverty were more susceptible to heat.Exposure to cold increased the risk of acute MI, and exposure to heat increased the risk of dying after an acute MI. Local area vulnerability should be accounted for as cities prepare to adapt to weather fluctuations as a result of climate change.