This study aimed to design energy-efficient systems for reactive distillation to simultaneously produce methyl tert-butyl ether (MTBE) and ethyl tert-butyl ether (ETBE) from mixed feeds of methanol and ethanol. In this work, two new designs are proposed. One is the individual production of each ether, involving two reactive distillation columns after feed alcohol separation, while the other for the co-production of both ethers in a single reactive distillation column without the alcohol separation. Rigorous simulations of the two proposed systems were conducted with varying ratios of the two alcohols in actual process streams. When the methanol feeding was dominant, the co-production system exhibited better performance than the individual ether production system. This was due to the lower temperatures inside the alcohol separation column, resulting in a lower relative volatility of methanol and increasing the heat duty in the alcohol separation column. However, when the amount of ethanol was higher than that of methanol, the individual production system outperformed the co-production system. This was attributed to the unfavorable reaction equilibrium of ETBE production, leading to a high internal flowrate in the co-production reactive distillation column. The external heat integration of each design can bring further reduction in energy consumption and CO2 emissions, but the results follow the same dependence on the feed alcohol ratio.