In this study, we investigated the association between wet-bulb globe temperature (WBGT) and gastroesophageal reflux disease (GERD) in different geographic regions of Taiwan in a large cohort. Participants (n = 120,424) residing in the four main geographical areas of Taiwan (North, Central, South and Eastern Taiwan) were enrolled from the Taiwan Biobank. Questionnaires were used to ascertain the presence of GERD based on self-reported physician diagnosis, and WBGT was assessed separately during working (8:00 AM to 5:00 PM) and noon (11:00 AM to 2:00 PM) periods. In Northern Taiwan, there is no significant association between WBGT and GERD during either the noon or working period. In Central Taiwan, the 1-, 3-, and 5-year WBGT values per 1℃ increase during the noon period (odds ratio [OR], 1.055 [95% CI 1.008-1.105]; 1.062 [95% CI 1.013-1.114]; 1.059 [95% CI 1.009-1.111]) and working period (OR, 1.089 [95% CI 1.034-1.146]; 1.092 [95% CI 1.037-1.150]; 1.084 [95% CI 1.031-1.139]) were significantly associated with GERD. Similarly, in Southern Taiwan, the 1-, 3-, and 5-year WBGT values per 1℃ increase during the noon period (OR, 1.292 [95% CI 1.236-1.351]; 1.323 [95% CI 1.261-1.389]; 1.386 [95% CI 1.316-1.460]) and working period (OR, 1.238 [95% CI 1.190-1.288]; 1.247 [95% CI 1.196-1.301]; 1.259 [95% CI 1.204-1.318]) were significantly associated with GERD. However, in Eastern Taiwan, the 1-, 3-, and 5-year WBGT values per 1℃ increase during the noon period were significantly associated with GERD (OR, 1.067 [95% CI 1.015-1.122]; 1.089 [95% CI 1.041-1.138]; 1.107 [95% CI 1.058-1.158]), whereas the 1-, 3-, and 5-year WBGT values per 1℃ decrease during the working period were significantly associated with GERD. Increases in average WBGT values were significantly associated with GERD during both the noon and working periods in Central and Southern Taiwan, and the impact of WBGT was much stronger in Southern Taiwan. While a similar result was found in Eastern Taiwan during the noon period, a reverse correlation was found during the working period. Our findings suggest that heat stress may be associated with GERD, although the impact may differ according to regional characteristics. The causal relationship could not be confirmed due to the cross-sectional design of the study. Further longitudinal studies are warranted to establish the relationship.