Background: Standard treatment of persistent pulmonary hypertension in neonates (PPHN) is inhaled nitric oxide (iNO), which is not available in Iran. Consequently, other drugs such as milrinone are prescribed. So far, no study has investigated the effect of inhaled milrinone on the management of PPHN.Our study was designed for better management of PPHN in the absence of iNO.Methods: In this randomized clinical trial, neonates with PPHN admitted Neonatal intensive care unit of Hazrat Ali Asghar and Akbarabadi hospitals were treated with intravenous dopamine infusion and randomly divided into two groups receiving injectable and inhaled milrinone. Neonates were evaluated by Doppler echocardiography, clinical status, and oxygen demand. Patients were also evaluated for clinical symptoms and mortality during follow-up. Results: A total of 31 infants with median age of 2 days (IQR: 4) were studied. There was a significant decrease in peak and mean pulmonary arterial pressure in both inhalation and infusion group following milrinone administration, with no statistical difference. (P=0.584 and 0.147, respectively). There was no significant difference among the frequency of tricuspid regurgitation and systolic blood pressure before and after treatment among two groups. Diastolic blood pressure was significantly lower in infusion group after treatment (P=0.020), however, the amount of decrease was not statistically significant among two groups (P=0.928). Overall, 83.9% achieved full recovery, of which 75% were among infusion groups while 93.3% were among inhalation group. (P=0.186)Conclusion: Inhaled milrinone can have similar effects with injected milrinone as an adjunct in the management of PPHN. Also, the results indicate similar safety for both intravenous and inhaled prescriptions. . Trial registration: IRCT code of this RCT trial is iIRCT20220130053890N1 and its Ethical verification code is IR.IUMS.FMD.REC.1400.493.