This work presents a feasibility study for an enzymatic reaction in a continuously operated reactive distillation column. As a model reaction, the transesterification of ethyl butyrate with n-butanol in the presence of lipase CALB was considered. For use in the distillation column, lipase CALB was immobilized by entrapment in a hydrophobic silica xerogel and introduced as granulate into the catalytic packing Katapak-SP-11. The reaction kinetics was experimentally determined for different concentration and temperature ranges and described by means of the MichaelisMenten double-substrate kinetic model in combination with the Arrhenius model. With these kinetic data, process simulations were carried out with an Aspen Custom Modeler nonequilibrium-stage model validated for a DN50 pilot-scale column. The concentration of n-butanol in the reactive section was maintained low to decrease the inhibiting effects on the enzyme. For an optimized setup and operating conditions, conversion rates of more than 90% were achieved for n-butanol and 26% for ethyl butyrate. These results clearly demonstrate that lipase CALB can be applied in a continuously operated reactive distillation column.