Nowadays, biodiesel has become a globally accepted renewable liquid fuel. The environmentally friendly enzymatic synthesis process is being widely researched. To solve the problem that production efficiency is low in enzymatic process, we optimized the structure of the static mixer by computational fluid dynamics (CFD) modeling. The optimal static mixer consists of 6 mixer units, and the length-diameter ratio of every mixer unit is 1.5. The enzymatic synthesis of biodiesel was conducted between waste cooking oil (WCO) and methanol by transesterification and esterification. The reaction conditions were also optimized in this designed static-mixed reactor. Under optimal conditions, the reaction time can save half time when compared with the traditional stirred reactor, which indicates that the static mixer has higher production efficiency. (C) 2020 Elsevier Ltd. All rights reserved.