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Ultrafiltration (UF) can effectively remove large particles, suspended solids, and colloidal substances from anaerobic digestate. However, membrane fouling is a technical challenge in the purification of the digestate by UF. In this study, polyethersulfone (PES) membranes with four pore sizes (50.0, 20.0, 10.0 and 5.0 kDa) were employed to filter anaerobic digestate from swine manure. The effects of temperature, transmembrane pressure (TMP), and cross-flow velocity (CFV) on flux were investigated. The purification effects and fouling characteristics of the four membranes were analyzed. The results revealed that the increase of temperature and CFV can effectively promote UF separation efficiency, but as the TMP exceeded 3.0 bar, the flux increase rates of the four membranes were almost zero. The larger membrane pore size caused the faster flux increase with the increase in pressure. During the batch experiment, the 20.0 kDa membrane showed the lowest flux maintenance ability, while the 5.0 kDa showed the highest ability due to the smaller pore size. All four membranes can effectively remove tetracyclines residues. Elements C, O, and S were the major membrane foulant elements. The dominant bacteria orders of membrane fouling were Pseudomonadales, Xanthomonadales and Burkholderiales. Compared with tap water and citric acid, the membrane cleaning by NaOH and NaClO showed higher flux recovery rates. The 50.0 kDa membrane achieved the best cleaning effects under all cleaning methods.