BACKGROUND Exhaled nitric oxide (ENO) has been shown to be a noninvasive marker of eosinophilic inflammation in asthmatic children. Few studies have evaluated the relationship between ENO levels and the clinical features of children with asthma. The aim of this study was to examine children attending a routine asthma clinic and evaluate the relationship between ENO levels and clinical parameters including decision making. METHODS Asthmatic children (n= 133, aged 5 to 14 years) attending a hospital asthma clinic were studied. ENO levels were measured and compared between subgroups of subjects according to recent symptoms, asthma control and treatment, and the clinician's decision (blinded to ENO levels) regarding further management. RESULTS ENO levels (median [IQR] ppb) were significantly elevated in children who had recent symptoms compared to those without recent symptoms (14.6 [6.5 to 45.3] vs. 6.0 [3.2 to 17.4], difference between medians 8.6, 95% confidence interval [CI] (1.8 to 13.9, p=0.004). ENO levels differed significantly between the controlled and uncontrolled subgroups (8.5 [4.2 to 26.4] vs. 26.4 [5.0 to 62.0], difference between medians 17.9, 95% CI 0.1 to 22.8, p=0.03) and between the three treatment decision subgroups (up, down, or unchanged; p < 0.001). CONCLUSIONS ENO levels are strongly related to the clinical features of childhood asthma and the clinical decision making process. To fully evaluate the role of ENO in the clinical management of asthma, this "proof of concept" study paves the way for prospective randomized trials of the inclusion of ENO levels in the decision making process in childhood asthma.