We evaluated the early and long-term prognosis of patients with a first non-Q-wave acute myocardial infarction (AMI) in relation to infarct site. Among 4,314 patients with a first AMI, 610 (14%) had a non-Q-wave AMI. Of them, 248 patients with anterior wall AMI were compared with 327 patients with inferior/lateral AMI. Baseline clinical characteristics were similar in both groups except for higher mean age in the anterior wall group. In-hospital complications were more common among patients with anterior wall AMI than in the inferior/lateral group. Patients with anterior wall AMI also had higher rates of in-hospital (15%), 1-year (12%), and 5-year (36%) postdischarge mortality compared with the inferior/lateral infarction group (10%, 6%, and 22%, respectively). The 1-year cardiac event rate (recurrent AMI and cardiac death) was significantly higher among the anterior wall AMI group than the inferior/lateral AMI group (14.2% and 4.8% respectively, p = 0.001). After adjustment for age, gender, systemic hypertension, diabetes mellitus, prior angina, and treatment with various medications, an increased risk for 1-year (odds ratio 1.31, 95% confidence interval [CI] 0.62 to 2.78) and 5-year mortality (relative risk 1.29, 95% CI 0.90 to 1.85) was observed, but it did not reach statistical significance. Anterior wall AMI location emerged as a predictor for higher 1-year cardiac event rate (odds ratio 3.15, 95% CI 1.59 to 6.78). These findings suggest that AMI location is an important prognostic variable for risk stratification of patients with a first non-Q-wave AMI.