Summary. Background: Cardiovascular risk factors for myocardial infarction (MI) are less frequent in younger than in older MI survivors. Therefore, the thrombotic component of MI may play a more important role at a young age. As activated protein C (APC) provides systemic anticoagulant and anti-inflammatory protection, a low plasma APC level may be an arterial thrombotic risk factor. Aim: To determine whether there is an association between reduced APC levels and early MI and severe coronary lesions. Methods: APC was measured in 231 young MI survivors and 231 controls. Results: Low APC levels were significantly associated with MI. Compared with the fourth quartile, the odds ratio (OR) for APC values in the first quartile was 3.7 [95% confidence interval (CI) = 2.1–6.4], and 3.2 (1.5–7.0) after adjustment for cardiovascular risk factors. Moreover, each decrease of 0.43 ng mL−1 (1 SD) in APC increased the OR 1.7 times (1.4–2.2), and 1.5 times (1.2–1.9) after adjustment for cardiovascular risk factors. Low APC levels were also associated with the number of coronary arteries affected and with the severity of coronary lesions (P < 0.001). Conclusions: There is a significant association between low circulating APC levels and both early MI and the extent and severity of coronary atherosclerosis, which might be related to the anticoagulant and anti-inflammatory properties of APC.