Vasoplegic syndrome is a form of vasodilatory shock that can occur before, during or after cardiopulmonary bypass (CPB). We introduce a strategy to reduce the incidence of early hypotension phenomena during Coronary Artery Bypass Graft (CABG) procedures. In this prospective cohort study, 100 patients underwent elective CABG with two perioperative CPB settings. The study group (50 patients) was managed with retrograde autologous priming (RAP), 3-minute stepwise for the institution of CPB, and pulsatile flow (PP). The control group (50 patients) was managed without RAP, with the rapid initiation of CPB, and non-pulsatile (NP) flow. The primary endpoints were MAP (mmHg), number of hypotensive phenomena (MAP < 50 mmHg for > 30 sec), the venous return volume on CPB (ml), the cardiac index (L/min/m2), hemoglobin (g/dL), indexed oxygen delivery (DO2i, ml/min/m2), the systemic vascular resistance index (SVRI, dynes s m2/cm5), number of 1-ml boluses of a vasoactive substance (norepinephrine), the positive fluid balance (ml), and the number of red blood cell units for transfusion. During CPB, the mean values in the study and control groups were as follows: MAP, 68± 7 vs 56 ± 7 (p-value, 0.0019); hypotensive phenomena, 3 ± 1 vs 8 ±2 (p-value, 0.019); venous return volume, 840±79 vs 1129 ±123 (p-value, 0.0017); cardiac index, 2.4 ± 0.4 vs 2.7 ±0.2 (p-value, 0.0023); hemoglobin, 9.13 ± 0.29 vs 7.8± 0.23 (p-value, 0.0001); DO2i, 301± 12 vs 276±23 (p-value, 0.0011); SVRI, 1879 ±280 vs 2210 ±140 (p-value, 0.0017); norepinephrine, 1±2 vs 8 ±3 (p-value, 0.0023); positive fluid balance, 750 ±212 vs 1450 ±220 (p-value, 0.005); and total number of red blood cell units for transfusion, 16 ±4.2 vs 27 ± 5.3 (p-value, 0.008). In this prospective cohort study, during CPB, the study group showed a better preservation of MAP, SVRI, and DO2i, and a reduction of vasoconstrictor use in a CPB setting with the RAP technique, 3-minute stepwise for the initiation of CPB and pulsatile pump flow, compared to the control group. Further studies are needed to validate this perioperative approach to CPB.