To evaluate the antifouling properties of the poly(ether sulfone) (PES)/sulfonated poly(ether sulfone) (SPES) blend membranes, the full-size membrane modules containing pure PES hollow fiber membranes and PES/SPES blend hollow fiber membranes were prepared and compared. First, a series of PES/SPES blend hollow fiber membranes with different SPES fraction were fabricated by a nonsolvent-induced phase separation (NIPS) process. The surface chemical compositions, morphology, surface wettability, permeability, and mechanical strength of the membranes were characterized. After assembling the module, the permeability and antifouling properties of the full-size modules were tested in a lab-scale evaluation system. Each full-size membrane module in this study included approximately 330 pieces of 1 m long hollow fiber membranes with an effective area of approximately 1 m(2). Three model foulants, i.e., sodium alginate (SA), humic acid (HA), and bovine serum albumin (BSA), and three real river water samples were used in evaluation of the antifouling properties. Hermia's models adapted to cross-flow ultrafiltration were used to investigate the fouling mechanism involved in the ultrafiltration of SA, HA, BSA, and river water samples. The results indicated that the membrane module containing the hollow fiber membranes with 10% of SPES (MD20-10) showed better antifouling properties than the membrane module containing pure PES hollow fiber membranes (MD22-0). In addition, the main fouling mechanism for all foulant is the complete blocking, intermediate blocking, or gel layer formation. Moreover, it was also confirmed that module MD20-10 possessed a sufficient chemical cleaning capability, which implied a promising potential for its practical application.