Introduction : Isolated systolic hypertension(ISH) is an important risk factor for stroke and cardiovascular mortality in elderly and is often refractory to treatment with established antihypertensive medications. ISH may have a relation to the endothelial dysfunction, characterized by decreased bioavailability of nitric oxide (NO). Molsidomine is a NO-releasing prodrug. The purpose of the present study was to assess the efficacy of a nitric oxide donor, molsidomine, in lowering systolic blood pressure (SBP) to a target of < 140 mmHg in the patients with uncontrolled ISH. Method : The subjects were 27 elderly patients with ISH. We defined uncontrolled ISH as SBP >140 mmHg and diastolic blood pressure (DBP) < 90 mmHg despite conventional treatments. All the subjects have undergone treatment with various regimens of conventional antihypertensive agents given in combination. Additionally, they received nitric oxide donor, molsidomine, 2 mg twice a day for continuous period of 6 months. Blood pressure was measured at three and six months after treatment. Results : Their mean age (짹 SD) was 73.4 짹 6.4 year (M:F=13:14). The mean values (짹 SEM) for systolic and diastolic blood pressure at baseline were 157 짹 2 mmHg and 73 짹 1 mmHg, respectively. After 3 and 6 months of treatment, molsidomine resulted in significant reduction in SBP with a daily dose of 4mg (mean change in SBP from baseline; -17.5 mmHg and -16.9 mmHg, respectively,p < 0.001). There were no significant changes in DBP (-1.4 mmHg and -3.1 mmHg, respectively) and heart rate. There were not any significant side effects from molsidomine treatment. Conclusion : A nitric oxide donor, molsidomine, significantly lowered SBP patients with uncontrolled ISH, suggesting that endothelial dysfunction may contribute to elevated blood pressure in such patients. The favorable efficacy of molsidomine on SBP occurred without diminishing in chronic treatment of ISH. Molsidomine may be considered for the treatment of uncontrolled ISH adjunct