Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. This study aimed to evaluate the change in RV pressure waveform in patients receiving a combination of inhaled epoprostenol and inhaled milrinone (iE&iM) before cardiopulmonary bypass (CPB) and to assess the safety of this approach with a matched case-control group. A prospective single-centre cohort study of adult patients undergoing cardiac surgery administered iE&iM through an ultrasonic mesh nebulizer. RV pressure waveform monitoring was obtained by continuously transducing the RV port of the pulmonary artery (PA) catheter. The final analysis included 26 patients receiving iE&iM. There was a significant drop in mean PA pressure (MPAP) (-4.8 ± 8.7, P= 0.010), systolic PA pressure (SPAP) (-8.2 ± 12.8, P= 0.003), RV end-diastolic pressure (RVEDP) (-2.1 ± 2.8, P < 0.001) and RV diastolic pressure gradient (RVDPG) (-1.7 ± 1.4, P < 0.001) after 17± 9 minutes of iE&iM administration. Patients also had a significant increase in RV outflow tract (RVOT) gradient (3.7 ± 4.7, P < 0.001), RV maximal rate of pressure rise during early systole (dP/dt max) (68.3 ± 144.7, P= 0.024), and left ventricular (LV) dP/dt max (66.4 ± 90.1, P < 0.001). Change in RVOT gradient was only observed in those with a positive pulmonary vasodilator response to treatment. Treatment with iE&iM did not present adverse effects when compared with a matched case-control group. Coadministration of iE&iM in cardiac surgery patients presenting with PH or signs of RV dysfunction is a safe and effective treatment approach in improving RV function. Appearance of a transient increase in RVOT gradient after iE&iM could be useful to predict response to treatment.