Azo compounds (azos) possess diverse exothermic properties that enable their application in numerous industrial processes, but these properties also engender a corresponding diversity of thermal hazard profiles. This study employed an innovative approach to determine the specific thermal reactions and decomposition hazard profiles of azos. Four typical azos (AIBN, AMBN, ABVN, and AIBME) were assessed using three thermal calorimetry techniques, and results were subsequently analyzed using a nonlinear optimization model. Thermal hazard analysis of small-scale experiments indicated that AIBN had a heat decomposition of 1247 J/g and a maximum pressure increase of 367 psig and thus exhibited more hazardous characteristics than did AMBN, ABVN, and AIBME. This study also obtained the relevant process safety parameters, time to maximum rate, onset and peak temperature, adiabatic temperature rise, and rate of pressure increase to use for later scaled-up applications. The findings of this study can be used to develop a predictive model for the thermal behavior of azos and to provide the necessary basis for the design and selection of precise treatment and appropriate safety systems.