Epidemiological studies show that increased plasma total homocysteine (tHcy) level was an independent risk factor of cardiovascular diseases. This study was aimed to investigate the relationship between tHcy level and prognosis of first-onset stroke in Chinese people. One hundred ninety six patients with first-onset ischemic stroke and ninety-five patients with first-onset hemorrhagic stroke were enrolled in this study. The patients were divided into two groups in terms of tHcy level (< 18 ?mol/L and ≥ 18 ?mol/L). The plasma tHcy level was detected by a high performance liquid chromatography method with fluorescence detection. All the patients underwent a 5-year follow-up. Survival analysis shows that the probability of death or new vascular events in the ischemic stroke patients with high tHcy level (≥ 18 ?mol/L) was significantly higher than that in the counterparts with lower tHcy level (< 18 ?mol/L) (50.9% and 28.7%, respectively, = 0.004). The relative risk of death or new vascular events was 2.363 (95% CI, 1.209 to 4.617, = 0.012) in ischemic stroke patients with high tHcy levels(≥ 18 ?mol/L) compared to those with a lower tHcy level (< 18 ?mol/L). The increased tHcy level was significantly associated with the risk of death or new vascular events (, 2.492, 95% CI, 1.148 to 5.407, = 0.021) in patients with ischemic stroke in the exclusion of the influence of other risk factors such as gender, age, body mass index, plasma cholesterol level, the history of hypertension, diabetes or smoking. However, in the patients with hemorrhagic stroke, there was no significant difference in the probability of death or new vascular events between patients with a high tHcy level and those with a lower tHcy level (33.3% and 28.2%, respectively, = 0.546). Increased tHcy level was an independent risk factor for a worse outcome in patients with first-onset ischemic stroke, but not in hemorrhagic stroke patients.