Reactive distillation (RD) integrates reaction and separation into a single process, resulting in dual process objectives: maximization of reactant conversion and product purity. Both the objectives, which are generally inconsistent, must be carefully considered in RD operation. Unfortunately, neither the conversion nor the purity are economically and reliably available. This work showed that the conversion could be inferred from multiple temperatures. A third-order two-variable nonlinear inferential model was recommended for synthesis of ethyl tert-butyl ether (ETBE) with a 10-stage RD column. The temperatures of the bottom reactive section and the reboiler were employed in the model. The experimental design, model identification and model test were investigated as well.