Background: Patients with ascites, hepatorenal syndrome, or both who have reduced plasma renin activity can benefit from midodrine, which is an α1-adrenergic agonist, by increasing the effective arterial blood volume by splanchnic vasoconstriction and decreasing nitrite as well as nitrate activity. We aimed at this research to assess the efficacy of midodrine in the managing refractory ascites caused by liver cirrhosis. Patients & Methods: The present case-control study included 100 patients who had refractory ascites due to liver cirrhosis. They were divided into 2 groups (50 each): The control group received standard medical treatment (SMT), and the midodrine group received SMT plus midodrine. Ascitic fluid study for calculation of SAAG and exclusion of spontaneous bacterial peritonitis was done for all participants. Patients were followed up one month of treatment. Results: After 1-month, mean values of body weight, paracentesis frequency, furosemide and spironolactone doses, S.creatinine were decreased significantly, mean arterial blood pressure and eGFR was significantly increased, among midodrine group (P<0.001). At cutoff value equal to 15 mg/ day, midodrine played a role in protection against hepatorenal syndrome. After 1 week a statistically significant positive correlation was revealed between midodrine dose and mean arterial blood pressure (p<0.001), Conclusions: The addition of midodrine to standard medical treatment (salt restriction and diuretics) in managing the refractory ascites with protection against hepatorenal syndrome at dose 15mg/day. So, it is considered safe adjuvant treatment for patients who had refractory ascites due to liver cirrhosis with little side effects