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Salmonella spp. exhibit prolonged survivability and high tolerance to heat in low-moisture foods. The reported thermal resistance parameters of Salmonella spp. in low-moisture foods appear to be unpredictable due to various unknown factors. We report here that temperature-dependent water activity (a w, treatment temperature ) plays an important role in the sharply increased thermal resistance of Salmonella enterica serovar Enteritidis PT 30 and its potential surrogate Enterococcus faecium NRRL B-2354. In our study, silicon dioxide granules, as carriers, were separately inoculated with these two microorganisms and were heated at 80°C with controlled relative humidity between 18 and 72% (resulting in corresponding a w,80°C values for bacteria between 0.18 and 0.72) in custom-designed test cells. The inactivation kinetics of both microorganisms fitted a log-linear model ( R 2 , 0.83 to 0.97). Reductions in the a w,80°C values of bacterial cells exponentially increased the D 80°C (the time needed to achieve a 1-log reduction in a bacterial population at 80°C) values for S . Enteritidis and E. faecium on silicon dioxide. The log-linear relationship between the D 80°C values for each strain in silicon dioxide and its a w,80°C values was also verified for organic wheat flour. E. faecium showed consistently higher D 80°C values than S . Enteritidis over the a w,80°C range tested. The estimated z aw (the change in a w,80°C needed to change D 80°C by 1 log) values of S . Enteritidis and E. faecium were 0.31 and 0.28, respectively. This study provides insight into the interpretation of Salmonella thermal resistance that could guide the development and validation of thermal processing of low-moisture foods. IMPORTANCE In this paper, we established that the thermal resistance of the pathogen S . Enteritidis and its surrogate Enterococcus faecium , as reflected by D values at 80°C, increases sharply with decreasing relative humidity in the environment. The log-linear relationship between the D 80°C values of each strain in silicon dioxide and its a w,80°C values was also verified for organic wheat flour. The results provide new quantitative insight into the way in which the thermal resistance of microorganisms changes in low-moisture systems, and they should aid in the development of effective thermal treatment strategies for pathogen control in low-moisture foods.