One of the major challenges in applying membrane technology is how to mitigate fouling, which decreases membrane productivity and lifetime. We previously developed a technique for preparing thin-film composite (TFC) polyamide membranes with submicron-patterned surfaces (via nanoimprint lithography), using interfacial polymerization techniques consistent with those used in the commercial production of reverse osmosis membranes. Herein, we present results from crossflow permeation experiments with these patterned and non patterned TFC membranes using aqueous NaCl/glycerol solutions, with and without bovine serum albumin (BSA) as a model protein foulant. The NaCl/glycerol/water fractionation properties of these membranes were not significantly affected by the imprinting process, and their separation performance is similar to that of commercially available materials. At a low transmembrane pressure with operation likely experiencing weak concentration polarization, the permeance decline is small with both imprinted and non-imprinted membranes. At a higher transmembrane pressure, however, a rapid flux decline was observed for the non-patterned membranes but not for the patterned ones. Furthermore, the patterned membranes recovered more of their initial pure water permeance after the fouling permeation experiments. These initial findings reinforce the prospect of improved long-term fouling mitigation due to surface patterning. In particular, our results suggest that even regular similar to 30 nm protruding surface patterns increase the flux with low protein deposition and may also lead to a looser structure (and, thus, easier removal) of any deposited surface protein layer.