The vacuum membrane distillation (VMD) process was applied to separate ethanol from a simulated ethanol–water solution using a commercial polytetrafluoroethylene (PTFE) membrane. The presence of ethanol in the ethanol–water solution with a 2 wt.% ethanol concentration at a temperature above 40 °C during the MD process may result in membrane failure due to an increase in the chance of the PTFE membrane wetting at high temperatures. Therefore, the operating temperature in this study was not higher than 35 °C, with an initial ethanol concentration up to 10 wt.%. This work focuses on optimizing the VMD operating parameters using the Taguchi technique based on an analysis of variance (ANOVA). It was found that the feed temperature was the most-affected parameter, leading to a significant increase in the permeation flux of the PTFE membrane. Our results also showed that the permeate flux was reported at about 24.145 kg/m2·h, with a separation factor of 8.6 of the permeate under the operating conditions of 2 wt.%, 30 °C, 60 mm Hg(abs), and 0.6 L/min feed (concentration, temperature, permeate vacuum pressure, and flow rate, respectively). The initial feed concentration, vacuum pressure, and feed flow rate have a lower impact on the permeation flux.