Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries.A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation.After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65-2.89), 2.40 (1.56-3.67), and 2.73 (1.83-4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (<15 μmol/L), the hazard ratios (95% confidence intervals) for IS in the highest tHcy category (≥30 μmol/L) were 4.96 (3.03-8.12), 6.11 (3.44-10.85), and 1.84 (0.52-6.46) in the total, males, and females participants, respectively. However, we did not observe a significant relationship between tHcy and the risk of coronary heart disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 μmol/L (27.92%) in patients with essential hypertension.Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels.