According to CDC's Foodborne Disease Outbreak Surveillance System database, from year 2007~2011, there have been eight outbreaks associated with low-moisture foods including nuts, cheese, cookie dough, and wheat snack foods involving Shiga toxin-producing Escherichia coli O157:H7 (STEC), which led to over 318 cases of foodborne illness. Yet, insufficient data on STEC thermal inactivation has been obtained in low-moisture foods. In this study, a differential scanning calorimeter is used to measure STEC inactivation kinetic parameters in low moisture environments. Six strains of outbreak related E. coli were individually grown on tryptic soy agar with yeast extract (TSAYE). The cells were harvested and inoculated into a moist buffer solution, simple model low-moisture matrix, and low-moisture foods (i.e. flour and peanut butter). Samples were individually heated using a differential scanning calorimeter (DSC). The DSC was able to achieve a reproducible and accurate thermal environment. Following heat treatment, microbial survivors were enumerated via plate count. The six strains showed greater thermal resistance levels in corn syrup, peanut butter and oat flour compared with buffer solution (p < 0.05). At the same processing duration, approximately 95°C was needed to reduce the outbreak strains of STEC in peanut butter by 5-log CFU/mL, whereas 85°C and 75°C were needed for corn syrup and buffer solution, respectively. D65°C ranged from 0.26-0.92 min minimum minute for the strains tested in buffer. Those same strains exhibited a 10-100 times increase in resistance in corn syrup (D65°C = 2.6-108.6 min). The measurement of the increased heat resistance of STEC in low moisture foods will improve science-based risk prevention by ensuring process lethality in these types of foods.