The role of hyperhomocysteinemia as independent risk factor for stroke needs to be confirmed. The aims of our study were to assess (i) the association between risk of stroke and increasing values of plasma homocysteine and (ii) the interaction between mild hyperhomocysteinemia and conventional vascular risk factors. We studied 161 consecutive patients with first-ever ischemic stroke classified using TOAST criteria and 152 neurologically healthy controls. Homocysteine was measured using high performance liquid chromatography (HPLC). Homocysteinemia was elevated in all stroke subtypes: 13.0+/-2.5 micromol/l in patients with cardioembolic disease, 13.9+/-5.4 micromol/l in those with small vessel diseases, 15.5+/-6.8 micromol/l in cases of undetermined stroke, and 17.8+/-13.5 micromol/l in patients with large vessel disease. Mean homocysteinemia was 8.10 micromol/l (SD=2.5) in controls. The logistic regression analysis showed that important independent risk factors for ischemic stroke were hypertension (p<0.0001; OR= 3.205; 95% CI, 1.788-5.742), hyperhomocysteinemia (p<0.0001; OR=1.425; 95% CI, 1.300-1562) and hyperlipidemia (p=0.018; OR=2.243; 95% CI, 1.147-4.385). Hyperhomocyst(e)inemia is an independent risk factor for all stroke subtypes and should be routinely measured and treated in stroke patients.