Membrane fouling is a critical problem limiting membrane performance and application lifetime. Zwitterionic polymers are highly resistant to irreversible membrane foulants because of their hydrated structure and charge neutral characteristics. The objectives of this study were to improve membrane antifouling performance with zwitterionic polymer modifications and to gain a better understanding of the factors affecting the process. We used polysulfone hollow fiber, instead of flat-sheet membranes, for the study because of its common industrial applications for ultrafiltration. Different characterization methods including scanning electron microscopy, nuclear magnetic resonance, attenuated total reflectance Fourier-transform infrared spectroscopy, contact angle goniometry, and cyclic filtration tests of deionized water and bovine serum albumin were applied to characterize the membrane and evaluate the performance of pristine and modified HFMs. Results showed that membrane fouling was significantly decreased by grafting the zwitterion carboxybetaine methacrylate (CBMA) via atom transfer radical polymerization. Positively charged [2(acryloyloxy)ethyl] trimethylammonium chloride with a quaternary amine end group and negatively charged 2-carboxyethyl acrylate with a carboxyl end group were grafted separately as charged polymer controls. These charged polymers improved the membrane antifouling property but not to the same extent as the membrane with the zwitterionic polymers. Compared with the pristine PSF HFMs, all modified membranes exhibited enhanced hydrophilicity and antifouling property.