The aim of this study was to investigate the initial clinical manifestations, laboratory data, complications, and outcomes of patients with pediatric-onset mixed connective tissue disease (MCTD) in Taiwan. We reviewed medical charts of patients younger than 18 years with a diagnosis of mixed connective tissue disease based on the criteria of Kasukawa (1) at the pediatric department of National Taiwan University Hospital from 1993 to 2008. A total of 12 patients were included. All of the patients were female. The mean age at disease onset was 10.7 years (range 6.5 to 14 years). The most common symptoms at disease onset were polyarthritis (7/12 patients) and Raynaud's phenomenon (7/12 patients). The clinical symptoms changed with time, and other symptoms encompassing the criteria for MCTD developed sequentially. Inflammatory manifestations (arthritis, fever, and skin rash) improved following treatment, whereas sclerodermatous features (sclerodactyly, esophageal disease, and vasculopathy) persisted and were often unresponsive to therapy. The organ involvement-free rates at 2 years, 5 years, and 10 years were 91.7%, 78.6%, and 52.4%, respectively. In this retrospective study, sclerodermatous changes of internal organs were a poor prognostic factor in our population, and we emphasize that long-term follow-up is necessary, and appropriate treatment should be applied to improve the outcomes.