Objective: This study was aimed to compare the effect of nebulized milrinone versus intravenous administration of milrinone in pulmonary hypertension patients who are candidates for open-heart surgeryMethod: A total of 32 patients candidates for open-heart surgery complicated by pulmonary hypertension were involved in this study and were arbitrarily classified into the nebulized milrinone group (n=16) and intravenous milrinone group (n=16) that they received drug after the opening of the cross-clamp of the aorta and before weaning off CPB. Heart rate (HR), cardiac output (CO), cardiac index (CI), stork volume (SV), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (mPAP), Systemic vascular resistance (SVR) pulmonary vascular resistance(PVR) and MAP/mPAP ratio, Extubation time, ICU stay and hospital stay were collected. Results: MAP and MAP/mPAP ratio increased significantly, however, mPAP was significantly lower in the nebulized milrinone group than in the intravenous milrinone group. Extubation time, ICU stay and hospital stays decreased significantly in the nebulized milrinone group than in the intravenous milrinone group.Conclusion: the administration of the nebulized milrinone before weaning off from CPB, accelerated and facilitated separation from CPB as it significantly decreases mPAP and preserves MAP.Trial registry: Registered under No. IRCT20201104049266N1