Heat-related diseases have become a significant public health concern. Studies have shown that susceptibility to heat varies among regions; however, most studies used aggregated data on emergency transport in the regions. The present study used a nationwide inpatient database in Japan and examined the association between regional differences in Wet Bulb Globe Temperature (WBGT) and in-hospital mortality in patients with a heat-related disease, with adjustment for individual-level characteristics. We retrospectively identified participants from the Japanese Diagnosis Procedure Combination inpatient database during the five warmest months of the year (May 1 to September 30) from 2011 to 2019. We calculated the long-term average daily maximum WBGT for the prefectures and categorized the prefectures into three areas (low-, middle-, and high-WBGT). We conduced multivariable logistic regression analyses to compare in-hospital mortality between the WBGT areas, adjusting for individual-level covariates (including age, sex, body mass index, and comorbidities). A total of 82,250 patients were admitted for heat-related diseases. The mean age was 63.2 (standard deviation, 25.0) years, and 63.7% were male. In the multivariable logistic regression analysis, the low-WBGT area had a higher in-hospital mortality than that had by the high-WBGT area (odds ratio, 1.32; 95% confidence interval, 1.15–1.52), whereas no significant difference was observed between the middle- and high-WBGT areas (odds ratio, 1.00; 95% confidence interval, 0.89–1.12). After adjusting for individual-level risk factors, in-hospital death was more likely to occur in patients with heat-related diseases in lower WBGT areas compared with those in higher WBGT areas.