Recently, several new biological drugs targeting severe asthma are on the market, and various studies on severe asthma have been reported worldwide. However, in Japan, the data are still limited regarding epidemiology and burden of disease on severe asthma. This study determined the prevalence, characteristics, and burden of disease of patients with severe asthma. This retrospective study (HO-16-16484) used a nationwide health care claims database. Severity of asthma was defined according to the treatment during the baseline period (April 1, 2014-March 31, 2015). Eligible patients were >15-65 years of age with asthma during the 12-month baseline period and were followed up for 12 months. End points included the prevalence, characteristics, exacerbation frequency, and patient behavior in patients with severe, moderate, or mild asthma. Risk factors for exacerbations were explored in patients with all levels of asthma severity and in those with severe asthma. Among the 16,107 patients with asthma, 2.4 (95% CI, 2.1-2.6) per 100 patients had severe asthma. During the baseline period, 130 (34.0%) of 382 patients with severe asthma had ≥1 asthma exacerbation. The exacerbation frequency was highest in patients with severe asthma, and most of the comorbidities increased in proportion to the asthma severity. During the follow-up period, exacerbation frequency increased with asthma severity. Approximately 70% of patients with severe asthma were treated at clinics, requiring outpatient visits ~10 times per year. Different exacerbation risk factors were identified between patients with all severity levels of asthma and those with severe asthma. With the severe asthma patients, experiencing exacerbations during the previous year was a risk factor for further exacerbations during the follow-up period. In Japan, 2.4% of patients with asthma have severe asthma, and there is a significant burden of disease in patients with severe asthma undergoing high-intensity treatment. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.