Ethyl tert-butyl ether (ETBE) is an alternative gasoline oxygenate that combines the blending properties of methyl tert-butyl ether (MTBE) and the renewability of ethanol. Technologically, the best means of synthesis utilizes reactive (or catalytic) distillation to maximize hydrocarbon conversion and energy efficiency while simultaneously producing a high-purity ether product. Mathematical models of reactive distillation are based on the conventional distillation process with supplementary equations added to model the reactions present. Ether-alkene-alcohol systems are highly nonideal in the liquid phase so that careful selection of physical property routines is required to ensure satisfactory simulation results. Column simulations performed here using both Pro/II and SpeedUp show excellent agreement with previously published experimental data for a MTBE system and also agree well with each other for both MTBE and ETBE systems. A homotopy analysis was performed on the tuned simulation models to determine the effects of key design and operating variables on column performance and, subsequently, to develop a design method for reactive distillation columns. Some unusual behavior was identified in ETBE reactive distillation columns compared with either MTBE columns or conventional distillation.