Low-temperature azo compounds are a new class of self-reactive materials commonly used as initiators and blowing agents. However, their structure contains a bivalent azo bond, which is quickly released at a high ambient temperature. Self-accelerating decomposition can result in a runaway reaction, fire, or explosion. Therefore, the main issue of this study was to ensure the thermal safety of 2,2'-azobis(2-methylpropionate) (AIBME) by itself and when dissolved in different solvents during manufacturing, storage, or transportation. Adiabatic experiments were performed to investigate the pressure and temperature stress effects on heat accumulation, runaway reaction, and catastrophic conditions. To perform a robust evaluation, both nonisothermal and isothermal conditions were employed to investigate the thermal stability of AIBME against potential hazards. The corresponding kinetic and thermokinetic parameters were obtained using the experimental data and a computational model. Finally, we determined experimentally an apparent activation energy of 109.0 kJ/mol under nonisothermal conditions, which can be used as a reference value for hazard prevention to minimize the cost of accidents caused by uncontrolled temperature conditions.