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Heat stroke (HS) induces disseminated intravascular coagulation (DIC); however, the prognostic significance of DIC in patients with HS has not yet been fully assessed in large populations. The aim of this study was to examine the prognostic significance of DIC in patients with HS using a nationwide registry.Data regarding HS were obtained and analyzed from three prospective, observational, multicenter HS registries (HSRs): 2010, 2012, and 2014. Univariate and multivariate analyses were performed to identify independent predictors of hospital death. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) diagnostic criteria, with a total score ≥ 4 implying a DIC diagnosis.In total, 705 (median age, 68 years; 501 men) were included in this study. Hospital mortality was 7.1% (50 patients). Multiple regression analysis revealed that hospital mortality was significantly associated with presence of DIC (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.09–4.27; p = 0.028). Mortality worsened as the DIC score increased, and increased remarkably to approximately 10% when the DIC score was 2.Presence of DIC was an independent prognostic factor of hospital mortality in patients with HS. Hematological dysfunction represents potential target for specific therapies in HS.Presence of DIC was an independent prognostic factor in HS.Mortality increased remarkably to approximately 10% even at a DIC score of 2.AT-III levels on admission in non-survivors were significantly lower than those of survivors.