Low-temperature helium plasma treatment followed by grafting of N-vinyl-2-pyrrolidone (NVP) onto poly(ether sulfone) (PES) ultrafiltration (UF) membranes was used to modify commercial PES membranes. Helium plasma treatment alone and post-NVP grafting substantially increased the surface hydrophilicity compared with the unmodified virgin PES membranes. The degree of modification was adjusted by plasma treatment time and polymerization conditions (temperature, NVP concentration, and graft density). The NVP-grafted PES surfaces were characterized by Fourier transform infrared attenuated total reflection spectroscopy and electron spectroscopy for chemical analysis. Plasma treatment roughened the membrane as measured by atomic-force microscopy, Also, using a filtration protocol to simulate protein fouling and cleaning potential, the surface modified membranes were notably less susceptible to BSA fouling than the virgin PES membrane or a commercial low-protein binding PES membrane. In addition, the modified membranes were easier to clean and required little caustic to recover permeation flux. The absolute and relative permeation flux values were quite similar for the plasma-treated and NVP-grafted membranes and notably higher than the virgin membrane. The main difference being the expected long-term instability of the plasma treated as compared with the NVP-grafted membranes. These results provide a foundation for using low-temperature plasma-induced grafting on PES with a variety of other molecules, including other hydrophilic monomers besides NVP, charged or hydrophobic molecules, binding domains, and biologically active molecules such as enzymes and ribozymes.