Homocysteine, a sulfur-containing amino acid, is an intermediate during the conversion of methionine to cysteine. Homocysteine can cause vascular injury and atherosclerotic plaque instability. In addition, homocysteine may be directly correlated with hyperlipidemia and lipoprotein(a) and inversely with high-density lipoprotein cholesterol. However, the results regarding the association of homocysteine level with subtypes of stroke and traditional risk factors for stroke have been inconsistent, perhaps due to ethnic differences. The aim of this study was to evaluate the role of serum homocysteine levels in Turkish patients diagnosed with atherosclerotic stroke and those with cardioembolic stroke. We measured homocysteine levels, traditional risk factors for stroke (hypertension, diabetes mellitus, and smoking) and lipoprotein(a) levels in 103 patients with large-vessel atherosclerotic stroke, 37 patients with cardioembolic stroke, and 37 controls with normal cranial magnetic resonance imaging. Only hypertension was found to be a risk factor in all patient groups (p = 0.001). Hyperhomocysteinemia (homocysteine level > or = 15.90 micromol/L) was more common in patients with large-vessel atherosclerotic stroke and cardioembolic stroke (p = 0.0435 and p = 0.007, respectively); nevertheless, it was found to be a risk factor only in patients with cardioembolic stroke (p = 0.023; odds ratio (OR): 5.745). Furthermore, in the patients with large-vessel atherosclerotic stroke, hyperhomocysteinemia was positively correlated with the lipoprotein(a) level (r = 0.227, p = 0.035). In conclusion, hyperhomocysteinemia is common in patients with large-vessel atherosclerotic stroke and cardioembolic stroke. More importantly, hyperhomocysteinemia is an independent risk factor only for cardioembolic stroke in the Turkish population.