Semibatch reactors (SBRs) are commonly used to conduct exothermic reaction in the pharmaceutical and fine chemical industries. From the thermal safety point of view, low MTSR (maximum temperature of synthesis reactions) is desirable. We have found that MTSR vs process temperature (T) profile favorably present S-shape in isothermal homogeneous SBRs involving highly exothermic or slow reactions. However, the criterion to determine the dependency of MTSR on T has been not thoroughly studied. In this work, such a theoretical criterion will be developed based on the fact that the derivative of MTSR to T is zero at the reaction temperature at which the lowest value of MTSR is obtained and experimentally validated by the hydrolysis reaction of acetic anhydride. To develop such a criterion, the quantitative relationship between the maximum accumulation X-ac,(max) and DamkOhler number (Da) for isothermal homogeneous semibatch reactions of arbitrary kinetic orders is first developed and numerically verified.