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Background: Vasoplegia or vasoplegic syndrome is a type of vasodilator shock that occurs in a large number of patients after cardiac surgery under a cardiac pulmonary pump, which can increase the incidence of complications and mortality in patients. Therefore, it is necessary to find a way to treat this disease. So, the aim of this study was to evaluate the effect of two doses of alpha-agonist midodrine on the prevention of vasoplegic syndrome induced by cardiopulmonary bypass. Methods: This study was performed on 135 patients undergoing cardiac surgery (45 cases in midodrine 5 mg, 45 cases in midodrine 10 mg, and 45 cases in control group) in Chamran hospital, Isfahan, Iran, in 2016. Patients were randomly assigned into three groups, the drugs were prescribed one hour before surgery, and the vital sign and complications were recorded in patients. Chi-square and ANOVA tests were used to compare the data. Findings: The mean blood pressure during the pump was higher in the midodrine 10 mg group than the other groups (5 mg midodrine and control) (P = 0.021); and the mean ephedrine administration in this group (15.33 mg) was also less than 5 mg midodrine (21.55 mg) and control (29.77 mg) groups (P = 0.012). Conclusion: Considering the high incidence of vasoplegic syndrome after cardiac surgery, administrating 10 mg of midodrine can improve clinical symptoms during the pump and reduce the need for vasopressor drugs, which can make better surgical results.