Nowadays, butanol is considered as biofuel. In this work, separation of butanol from aqueous solution was carried out by vacuum membrane distillation with polytetrafluoroethylene membrane, using mechanical vapor compression on the downstream. Higher flow rates could promote membrane separation with higher total flux and higher separation factor, thus influencing butanol separation. Membrane fouling was observed which exerted a substantial effect on the membrane separation performance with a real fermentation broth. Compared to the traditional distillation process, this procedure is more cost-effective due to similar to 50 % reduced energy consumption.