Background: Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased cardiac index, and characterized by inadequate response to standard doses of vasopressors, and increased morbidity and mortality. It occurs in 9%-44% of cardiac surgery patients after cardiopulmonary bypass (CPB). The underlying pathophysiology following CPB consists of resistance to vasopressors (inactivation of Ca 2+ voltage gated channels) on the one hand and excessive activation of vasodilators (SIRS, iNOS, and low AVP) on the other. Use of angiotensinconverting enzyme inhibitor (ACE-I), calcium channel blockers, amiodarone, heparin, low cardiac reserve (EF < 35%), symptomatic congestive heart failure, and diabetes mellitus are the perioperative risk factors for VPS after cardiac surgery in adults. Till date, there is no consensus about the outcome-oriented therapeutic management of VPS. Vasopressors such as norepinephrine (NE; 0.025-0.2 µg/kg/min) and vasopressin (0.06 U/min or 6 U/h median dose) are the first choice for the treatment. The adjuvant therapy (hydrocortisone, calcium, vitamin C, and thiamine) and rescue therapy (methylene blue [MB] and hydroxocobalamin) are also considered when perfusion goals (meanarterial pressure [MAP] > 60-70 mmHg) are not achieved with nor-epinephrine and/or vasopressin.Aims: The aims of this systematic review are to collect all the clinically relevant data to describe the VPS, its potential risk factors, pathophysiology after CPB, and to assess the efficacy, safety, and outcome of the therapeutic management with catecholamine and non-catecholamine vasopressors employed for refractory vasoplegia after cardiac surgery. Also, to elucidate the current and practical approach for management of VPS after cardiac surgery.Material and Methods: "PubMed," "Google," and "Medline" weresearched, and over 150 recent relevant articles including RCTs, clinical studies, meta-analysis, reviews, case reports, case series and Cochrane data were analyzed for this systematic review. The filter was applied specificallyusing key words like VPS after cardiac surgery, perioperative VPS following CPB, morbidity, and mortality in VPS after cardiac surgery, vasopressors for VPS that improve outcomes, VPS after valve surgery, VPS after CABG surgery, VPS following complex congenital cardiac anomalies corrective surgery, rescue therapy for VPS, adjuvant therapy for VPS, definition of VPS, outcome in VPS after cardiac surgery, etiopathology of VPS following CPB. This review did not require any ethical approval or consent from the patients.Results: Despite the recent advances in therapy, the mortality remains as high as 30%-50%. NE has been recommended the most frequent used vasopressor for VPS.It restores and maintain the MAP and provides the outcome benefits. Vasopressin rescue therapy is an alternative approach, if catecholamines and fluid infusions fail to improve hemodynamics. It effectively increases vascular tone and lowe...