Heatstroke is a life-threatening event that affects people worldwide. Currently, there are no established tools to predict the outcomes of heatstroke. Although the Sequential Organ Failure Assessment (SOFA) score is a promising tool for judging the severity of critically ill patients. Therefore, in this study, we investigated whether the SOFA score could predict the outcome of patients hospitalized with severe heatstroke, including the classical and exertional types, by using data from a Japanese nationwide multicenter observational registry. We performed retrospective subanalyses of the Japanese Association for Acute Medicine heatstroke registry, 2019. Adults with a SOFA score ≥ 1 hospitalized for heatstroke were analyzed. We analyzed data for 225 patients. Univariate and multivariable analyses showed a significant difference in the SOFA score between non-survivors and survivors in classical and exertional heatstroke cases. The area under the receiver operating characteristic curve were 0.863 (classical) and 0.979 (exertional). The sensitivity and specificity of SOFA scores were 50.0% and 97.5% (classical), 66.7% and 97.5% (exertional), respectively, at a cutoff of 12.5, and 35.0% and 98.8% (classical), 33.3% and 100.0% (exertional), respectively, at a cutoff of 13.5. This study revealed that the SOFA score may predict mortality in patients with heatstroke and might be useful for assessing prognosis.