Abstract Background: Low systemic vascular resistance during and immediately after cardiac surgery in which cardiopulmonary bypass is utilized is a well-known phenomenon, characterized as vasoplegia, which appears with an incidence ranging between 5% and 15%. The etiology is not completely elucidated and the clinical importance remains speculative. Methods: In this prospective clinical trial, we assessed the incidence of postoperative low systemic vascular resistance in 800 consecutive patients undergoing elective coronary artery bypass grafting and/or valve replacement. We have attempted to identify the predictive factors responsible for the presence of low systemic vascular resistance and we have examined the subsequent postoperative outcome of those patients who developed early postoperative vasoplegia. The severity of vasoplegia was divided into three groups according either to the value of systemic resistance and/or the dose of vasoconstrictive agents necessary to correct the hemodynamic. Results: Six hundred twenty-five patients (78.1%) did not develop vasoplegia, 115 patients (14.4%) developed a mild vasoplegia, and 60 patients (7.5%) suffered from severe vasoplegia. Low systemic vascular resistance did not affect hospital mortality but was the cause for delayed extubation and prolonged stay on the intensive care unit IICU). Logistic regression analysis identified temperature and duration of cardiopulmonary bypass, total cardioplegic volume infused, reduced left ventricular function, and preoperative treatment with angiotensin-converting enzyme (ACE)-inhibitors, out of 25 parameters, as predictive factors for early postoperative vasoplegia. Conclusion. The occurrence of low systemic vascular resistance following cardiopulmonary bypass is as high as 21.8%. The etiology of this clinical condition is most probably multifactorial. Mortality is not affected by vasoplegia, but there is a trend to higher morbidity and prolonged stay in the ICU.