Inhaled nitric oxide (iNO) can reduce pulmonary arterial hypertension and improve oxygenation in some patients with severe respiratory or heart failure. Despite this, iNO has not been found to improve survival. This study aimed to perform a local practice audit to assess the mortality predictors of critically ill patients who had received iNO as therapy for pulmonary hypertension and respiratory or heart failure. A retrospective audit in a single tertiary centre intensive care unit of patients receiving iNO was conducted between 2004 and 2009. The indications for iNO use, comorbidities, severity of illness, organ function, oxygenation, Sequential Organ Failure Assessment scores, patterns of iNO use, adverse events and outcomes were reviewed. In 215 patients receiving iNO, improvement in oxygenation after one hour from iNO commencement did not predict either intensive care unit (P = 0.36) or hospital (P = 0.72) mortality. The independent risk factors for intensive care unit mortality were worsening Sequential Organ Failure Assessment scores within 24 hours of commencing iNO (adjusted odds ratio 1.07, 95% confidence interval 1.05 to 1.18), the Charlson Comorbidity Score (adjusted odds ratio 1.49, 95% confidence interval 1.16 to 1.91) and the peak methaemoglobin concentration in arterial blood while receiving iNO (adjusted odds ratio 2.67, 95% confidence interval 1.42 to 4.96). Inhaled nitric oxide as salvage therapy for severe respiratory failure in critically ill patients is not routinely justified. Increased methaemoglobin concentration during iNO therapy, even when predominantly less than 3%, is associated with increased mortality.