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Background: Increased plasma homocysteine (Hcy) levels are a risk factor for stroke and can be reduced with folic acid therapy. Therefore, it is extremely important for patients with hyperhomocysteinemia (HHcy) to obtain the normal level of Hcy after folate intervention. Thus far, few studies have reported the effective rate defined as percentage of patients who achieved normal plasma Hcy levels after folic acid therapy., Objectives: The present study aimed to investigate the effective rate of folic acid for the treatment of HHcy and the impact of plasma baseline Hcy levels and the compliance of oral folic acid on the efficacy., Methods: A total of 858 patients with HHcy were treated with oral folic acid (5 mg/d) for 3 months. Fasting blood samples collected at baseline and at the end of treatment were assayed for plasma Hcy levels., Results: After 3 months of treatment, the plasma Hcy levels of 484 patients were reduced to below the normal levels (15 μmol/L), corresponding to an effective rate of 56.41%. The average of Hcy levels decreased by 28.05%. The effective rates of folic acid therapy in a mild Hcy elevated group and an intermediate Hcy elevated group were 61.34% and 27.78%, respectively (p = 0.000). The effective rates among patients with good and poor compliance of oral folic acid were 65.29% and 35.18%, respectively (p = 0.000)., Conclusions: More than 40% patients with HHcy failed to reach the normal range (5-15 μmol/L) after 3 months of folic acid supplementation. Further prospective studies are warranted to explore the reasons for failure.