Aim Inhaled nitric oxide (iNO) is the most common, although expensive, therapy for persistent pulmonary hypertension of the newborn and hypoxaemic respiratory failure. With significant variation in iNO delivery practices amongst clinicians, this study aimed to assess the effectiveness of a stewardship programme in increasing clinician compliance with revised, standardised protocols and to measure the impact of compliance on iNO therapy use. Methods Initiation and weaning protocols for iNO were introduced to the neonatal intensive care unit at The Centenary Hospital on 01 March 2016. A 2‐year stewardship programme was utilised to assess protocol compliance and the resulting iNO usage impacts were measured. A combined retrospective and prospective study from 1 March 2014 to 28 February 2018 was conducted to compare the patterns of iNO utilisation between the pre‐ and post‐stewardship cohorts. Results The pre‐stewardship cohort incorporated 18 neonates, receiving 19 iNO treatment episodes, and 18 neonates, receiving 21 iNO treatment episodes, in the post‐stewardship cohort. No significant difference in patient demographics was determined. Compliance with the protocols improved from 61% in year 1 to 88% in year 2 of the stewardship programme. Significant reductions were observed in median total hours of iNO therapy per patient (P = 0.0014) and in median time from therapy initiation to initial wean (P < 0.0001). The cost of iNO therapy reduced 52% during the stewardship programme with no increase in adverse patient outcomes. Conclusion An iNO stewardship programme could be safely implemented in any NICU leading to increased protocol compliance with a beneficial reduction in iNO usage and cost.