Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty-seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, β-agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, β-agonist use and lung function only. Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, β-agonist use, FEV1% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 µg (26–607 µg); FeNo group: 316 µg (200–500 µg) and had significantly higher MEF50% predicted (control group: median (interquartile range): 68.5% (55.8–83.1%); FeNO group: 83.2% (62.9%–98.3%). At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (β = −8.77; P < 0.002), β-agonist use 2 weeks prior to a visit (β = 0.11; P < 0.05), asthma symptoms (β = 0.02; P < 0.0001), and bronchial hyperresponsiveness (β = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc.