Background: The aim of this study was to explore whether serum baseline tryptase (sBT) levels might be a useful marker not only for the accurate diagnosis of childhood asthma, but also for the prediction of disease severity. Methods: A total of 114 asthmatic children were enrolled in this study, 36 of whom had mild intermittent asthma, 38 had mild persistent asthma, and 40 had moderate to severe persistent asthma. Additionally, 34 age-matched healthy children were enrolled as controls. The sBT levels of these populations were measured using a fluoroenzymeimmunoassay kit. The diagnostic performance of sBT levels and their correlation with asthma severity were systematically investigated using receiver operating characteristic (ROC) analysis and correlation analysis. Results: Children with mild and moderate to severe persistent asthma had significantly increased sBT levels as compared to those with mild intermittent asthma and healthy controls. ROC analysis further demonstrated that sBT levels not only appear to be highly sensitive and specific for distinguishing asthmatic children from healthy controls, but also show good accuracy for the differentiation of various asthmatic subgroups. Correlation analysis revealed that in all asthmatic subgroups sBT levels were significantly correlated with a variety of key markers that reflect the disease severity of asthma, including childhood asthma control test scores, serum IgE and interleukin-13 levels, blood eosinophil counts, and pulmonary test parameters. Conclusions: sBT levels may have a potential use in supporting a diagnosis of asthma in children and as a predictor of disease severity.