The transesterification of ethyl butyrate with 1-butanol to give butyl butyrate catalyzed by Novozym 435 was performed in a batch slurry reactor and in a packed-bed microreactor. The observed reaction rate is strongly influenced by external and intra-particle transport limitations. However, the packed-bed microreactor allows for higher specific enzyme loading and shorter diffusion pathway than that of the batch reactor, therewith enabling higher overall conversion and higher reaction rate per unit of catalyst volume. Novozym 435 showed to be stable up to 80 °C in the packed-bed microreactor, with low reactant molar ratio (ethyl butyrate:1-butanol) being desirable to achieve higher conversions. Total conversion was achieved in approximately 4 min residence time giving 0.04 mol/L of product, while in batch more than 30 min were needed for maximum conversion of 87%. Continuous 12 h operation at 70 °C was performed without noticeable deactivation of the enzymes. Moreover, the same packing was reused for several days without indicating any activity loss. To the best of our knowledge, this is the first engineering paper on enzymatic microreactors that gives a complete kinetic description, clear-cut benchmarking to a batch process, study on enzyme stability, and an outline on enzymatic microreactor production performance.