In this work, a reactive distillation column in which chemical reactions and separations occur simultaneously is applied for the synthesis of tert-amyl ethyl ether (TAEE) from ethanol (EtOH) and tert-amyl alcohol (TAA). A rate-based kinetic model for liquid-phase etherification and an equilibrium stage model for separation are employed to study the reactive distillation. The calculation is carried out using the commercial software package, Aspen Plus. Simulations are performed to examine the effects of design variables, i.e., a number of rectifying, reaction and stripping stages on the performance of reactive distillation column. It has been found that an optimal column configuration for the TAEE production under the study is designed with no rectifying, 4 reaction and 8 stripping stages. With such an appropriate specification of the reactive distillation column, the effects of various operating variables on the TAA conversion and TAEE selectivity are further investigated and the results have shown that the reflux ratio and operating pressure are the most important factors to the operation of the reactive distillation.