Enzymatic Reactive Distillation (ERD) is a bioreactive process, in which enzymes are immobilized on column internal surface, and helps to overcome chemical reaction and phase equilibrium limitations. The activation of enzymes by ultrasound (US) leads to ultrasound-assisted ERD (US-ERD) which might display more eco-efficiency than standard processing of valuable chemicals. Reaction rate improvements of more than 50% could be achieved by the assistance of US. An US-ERD process for the synthesis of butyl butyrate (10 kilotons per year, 99 wt% purity) was designed. A techno-economic evaluation via process optimization was carried out to minimize the annual costs, by using an evolutionary algorithm. The techno-economic evaluation shows that the US-ERD process and the ERD share nearly equal costs. Installation costs of the US equipment are high but they are compensated by a 12% lower reactive section height and a 7% lower total height of the US-ERD column in comparison to ERD. (C) 2017 Elsevier Ltd. All rights reserved.