Hydrolysis of isobutyric anhydride suffers from the mass transfer issues associated with the inherent partial miscibility of the participating reactants in a certain concentration temperature space. Hence, activity-based models are developed and used to describe the phase equilibrium behavior and the kinetics. In this work, the experimental and modeling approaches employed to study the kinetics in the single-and two-phase regions are presented. The solvation effects or the effect of autocatalysis on the rate of hydrolysis are studied. A discussion on the use of external acid catalysts/autocatalysis to enhance the rate of this reaction, especially in the two-phase region, and its application as a potential hazard identification tool is also presented.