Beta-adrenoceptor agonists (beta-agonists), in widespread clinical use for obstructive lung disease, have been associated with an increased risk of cardiovascular mortality. The objective of this study was to assess the association between incident myocardial infarction and the use of inhaled beta-agonists. We performed a case-control study within the Group Health Cooperative of Puget Sound (GHC). Between 1989 and 1994, we identified 1,444 cases with an incident myocardial infarction and 4,094 control subjects frequency-matched on age, sex, hypertension, and index date. The computerized pharmacy database of the health maintenance organization (HMO) was used to assess the use of beta-agonists by metered dose inhaler (MDI). Cardiovascular risk factor information was obtained from medical record review. In comparison to subjects who did not fill a beta-agonist prescription, subjects who had filled one beta-agonist MDI prescription in the 3 mo prior to their index date had an elevated estimated risk of myocardial infarction (adjusted odds ratio [OR]: 1.67 [95% CI, 1.07 to 2.60]). The elevated risk was limited to those subjects who had a history of cardiovascular disease (adjusted OR: 3.22 [95% CI, 1.63 to 6.35]) and among those with cardiovascular disease, to new users of beta-agonists (adjusted OR: 7.32 [95% CI, 2.34 to 22.8]). There was no dose-response relationship between beta-agonists use and risk of myocardial infarction. In this study, new use of beta-agonists was associated with an increased risk of myocardial infarction, although we cannot determine if the association is causal. Our study suggests that clinicians should exercise caution when giving an initial beta-adrenoceptor agonist prescription to patients with cardiovascular disease.