Large-scale CFD studies are currently lacking in membrane distillation due to high computational overhead. This study utilizes a validated CFD model for vacuum membrane distillation and reduces the order of the model to enable prototype scale simulations. Different module designs were considered: a baseline flat sheet membrane module, a spacer-filled channel, a wavy channel, and a wavy channel with embedded stiffeners. Different lengths (330 mm, 660 mm, and 990 mm) were studied to simulate lab to prototype upscaling. Large Eddy Simulations were run in the laminar (Re 900) and turbulent (Re 3600) flow regimes. For Re 900, cases with geometric alterations (wavy membrane, spacer-filled channel) locally outperformed the baseline case within the first 330 mm before axial temperature polarization equilibrated the performance between the baseline and altered channels. The improvement in local performance was seen over the whole 990 mm length at Re 3600, culminating in a 35–40 % flux improvement versus the baseline at Re 3600 versus a 0–35 % difference at Re 900. Axial temperature polarization was mitigated using heat injection, showing a 5 % flux drop as length tripled compared to a 20–27 % decline. Higher operational Reynolds numbers should be considered cautiously for increasing pressure drop and violating the liquid entry pressure limit for wetting.