Dimethyl sulfoxide (DMSO) is a widely used solvent often employed for a variety of organic syntheses. It is stable at room temperature, can dissolve many types of organic materials, and is miscible in water. However, upon heating in a closed system under conditions typically achievable in a commercial chemical plant, DMSO undergoes significantly exothermic and hazardous decomposition which could realistically lead to a pressure vessel explosion unless adequate protection layers were installed, possibly including a pressure relief system. This study provides calorimetry data from several apparatus and methods to characterize the decomposition to aid in assessing hazards and designing protection systems. (c) 2016 American Institute of Chemical Engineers Process Saf Prog 35: 374-391, 2016