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Membrane distillation (MD) is a potentially economical water treatment process that can enhance water recovery and reduce the volume of concentrated brines produced by desalination processes. However, MD is yet to be implemented commercially because of several knowledge gaps that prevent scaling up MD. To use scaled up MD systems for the treatment of high salinity water, it is also vital to understand the effect of feed concentration and module size on water flux and energy consumption in MD compared to other water treatment technologies. Existing research and literature on improvements in MD have mainly been focused on analyzing MD in bench-scale systems. Very few studies have explored the effect of scale up on energy efficiency and water quality in MD. Furthermore, while several studies have explored new membrane materials in bench-scale systems, the applicability of new membranes in pilot-scale systems is often not investigated. The focus of this work is to highlight the key differences in operation between bench and pilot-scale that would enable efficient use of bench-scale data in predicting water flux and energy consumption in pilot-scale systems without the need for additional pilot-scale experiments. The activity of water is generally a weak function of salinity. However, because of the energy-efficient design of pilot-scale MD, the transmembrane temperature difference and hence vapor pressure difference in a pilot-scale system is small. Thus, increasing the feed salinity can lead to a negative or negligible vapor pressure difference in pilot-scale systems. The implications of reduced driving force when treating high feed salinity water on the minimum energy required in pilot-scale MD were explored in this work and compared with conventional processes such as reverse osmosis (RO) A model was developed to predict water flux and energy consumption of pilot-scale membrane distillation using a single parameter called membrane distillation coefficient determined