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Initiated chemical vapor deposition (iCVD) was used to coat two porous substrates (i.e., hydrophilic cellulose acetate (CA) and hydrophobic polytetrafluoroethylene (PTFE)) with a crosslinked fluoropolymer to improve membrane wetting resistance. The coated CA membrane was superhydrophobic and symmetric. The coated PTFE membrane was hydrophobic and asymmetric, with smaller pore size and lower porosity on the top surface than on the bottom surface. Membrane performance was tested in membrane distillation experiments with (1) a high-salinity feed solution and (2) a surfactant-containing feed solution. In both cases, the coated membranes had higher wetting resistance than the uncoated membranes. Notably, wetting resistances were better predicted by LEP distributions than by minimum LEP values. When LEP distributions were skewed towards high LEP values (i.e., when small pores with high LEP were greater in number), significant (measurable) salt passage did not occur. For the high-salinity feed solution, the coated PTFE membrane had greater wetting resistance than the coated CA membrane; thus, reduced surface pore size/porosity (which may reduce intrapore scaling) was more effective than increased surface hydrophobicity (which may reduce surface nucleation) in preventing scaling-induced wetting. Reduced pore size/porosity was equally as effective as increased hydrophobicity in resisting surfactant-induced wetting. However, reduced porosity can negatively impact water flux; this represents a permeability/wetting resistance tradeoff in membrane distillation – especially for high-salinity applications. Membrane and/or membrane coating properties must be optimized to overcome this permeability/wetting resistance tradeoff and make MD viable for the treatment of challenging streams. Then, increasing hydrophobicity may not be necessary to impart high wetting resistance to porous membranes. These results are important for future membrane design, especially as manufacturers seek to replace perfluorinated materials with environmentally friendly alternatives.