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The hypothesis was that prediction of asthma exacerbations in children is possible by profiles of exhaled volatile organic compounds (VOCs), a non-invasive measure of airway inflammation.To study: 1) whether VOCs in exhaled breath are able to predict asthma exacerbations, and: 2) the time course and chemical background of the most predictive VOCs.A prospective study was performed in 40 children with asthma during one year. At standard 2-month intervals, FeNO, VOC profiles in exhaled breath samples, lung function and symptoms were determined in a standardised way. VOC profiles were analysed by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS).16 out of 40 children experienced an exacerbation. With support vector machine analysis, the most optimal model of baseline measurements versus exacerbation within patients was based on 6 VOCs (correct classification 96%, sensitivity 100%, specificity 93%). The model of baseline values of patients with compared to levels of patients without an exacerbation consisted of 7 VOCs (correct classification 91%, sensitivity 79%, specificity 100%). FeNO and lung function were not predictive for exacerbations.This study indicates that a combination of different exhaled VOCs is able to predict exacerbations of childhood asthma.