Studies on the relationship between fibrinolysis and arterial thrombosis have been conflicting. Previously, we demonstrated that hypofibrinolysis, as measured by a plasma-based assay, increased the risk of venous thrombosis. The present study investigated increased clot lysis time (CLT) measured with the same assay as a risk factor for myocardial infarction in a case-control study including 421 men with a first myocardial infarction and 642 controls below 70 years. CLT was strongly associated with body-mass index, lipid levels, blood pressure and C-reactive protein. Overall, risk of myocardial infarction was 1.4-fold (95% confidence interval (CI) 1.0-1.9) increased for CLT in the fourth quartile (longest CLT) compared with the first quartile. After adjusting for cardiovascular risk factors this risk disappeared (OR 1.0, 95%CI 0.6-1.5). In men aged <50 years the association was pronounced (OR 3.2, 95%CI 1.5-6.7). After adjustment for cardiovascular risk factors the risk was nearly twofold increased (OR 1.8, 95%CI 0.7-4.8). In men aged > or = 50 years, no clear association between CLT and risk of myocardial infarction was found. Our study suggests that hypofibrinolysis increases the risk of a first myocardial infarction in young men, although the causality of this association remains to be determined.