A new system combining a microreactor and a microcalorimetric chip was investigated. The small size of the microreactor channel permits maintaining isothermal conditions necessary for the kinetic characterization of highly exothermic reactions. These conditions are not easily obtained in classical calorimetric systems. The degree of mixing in the microchannel, which plays an important role for the characterization of fast reactions, was determined experimentally using an iodate–iodide system and confirmed by calculations. The calorimetric system was calibrated by performing the neutralization reaction of NaOH with H2SO4 in the microchannel. Several optimizations of the microreactor design allowed to raise the sensitivity of the system and to preheat the entering fluids. The results obtained were repeatable and reproducible. The establishment of the heat balance and the evaluation of the various resistances allowed a better global understanding of the system.