The present paper deals with thermal runaway risk of esterification reaction in semibatch reactor. It identifies thermal runaway conditions for the esterification of 2-butanol (2B) and propionic anhydride (PA) with sulfuric acid (SA). The autocatalytic kinetic model of esterification of 2B and PA with SA was obtained by the experiments. A new boundary diagram was proposed for the autocatalytic parallel reactions. Then, the combined boundary diagram considering the target temperature and maximum allowable temperature was used to define the critical conditions for the thermal runaway. The conditional probability of thermal runaway for esterification of 2B and PA with SA was calculated by Monte Carlo simulations.