Knowledge of the decomposition reactions of chemicals when tested neat versus in mixtures with various solvents is essential for process safety studies. The decomposition of several mercaptotetrazole derivatives was studied by differential scanning calorimetry, both neat and in seven different solvents. Most mixtures exhibited destabilization of the chemical in the solvent compared with the neat material, resulting in a lower decomposition onset temperature in the mixture. It was demonstrated that the decomposition mechanism and kinetics changed significantly when these chemicals were mixed with solvents. The highly variable effects on thermal stability from mixing thermally unstable chemicals with solvents demonstrates the value of thermal stability testing of reaction mixtures as integral part of process hazard identification.