Limited evidence suggests that persons with conditions such as diabetes, hypertension, congestive heart failure, and respiratory conditions may be at increased risk of adverse cardiovascular morbidity and mortality associated with ambient air pollution. The authors collected data on over 4 million emergency department visits from 31 hospitals in Atlanta, Georgia, between January 1993 and August 2000. Visits for cardiovascular disease were examined in relation to levels of ambient pollutants by use of a case-crossover framework. Heterogeneity of risk was examined for several comorbid conditions. The results included evidence of stronger associations of dysrhythmia and congestive heart failure visits with comorbid hypertension in relation to increased air pollution levels compared with visits without comorbid hypertension; similar evidence of effect modification by diabetes and chronic obstructive pulmonary disease (COPD) was observed for dysrhythmia and peripheral and cerebrovascular disease visits, respectively. Evidence of effect modification by comorbid hypertension and diabetes was observed in relation to particulate matter less than 10 microm in aerodynamic diameter, nitrogen dioxide, and carbon monoxide, while evidence of effect modification by comorbid COPD was also observed in response to ozone levels. These findings provide further evidence of increased susceptibility to adverse cardiovascular events associated with ambient air pollution among persons with hypertension, diabetes, and COPD.