Effects of membrane morphology and operating conditions on the performance of cross-flow microfiltration are studied. Three kinds of membranes with the same mean pore size of 0.1 μm are selected for filtration experiments. They are MF-Millipore, Durapore and Isopore membrane. The variations of cake and membrane resistance during filtration using these membranes are measured and used for blocking analysis. Although complete pore blocking occurs, Isopore membrane results in the highest filtration rate due to less cake formation. The filtration rate of Durapore membrane is lower than that of Isopore membrane. It is because, more particles deposit on the surface of Durapore membrane to form filter cake. MF-Millipore membrane results in the lowest filtration rate due to the most cake formation and a serious pore blocking. The pore structures of each membrane are modeled in order to understand the mechanisms of pore blocking. At the initial stage of filtration, a standard blocking occurs in MF-Millipore membrane, an intermediate blocking in Durapore membrane, and a complete blocking in Isopore membrane. These blocking models are transferred to cake filtration after 10 min for all kinds of membranes. The pore blocking in each membrane is also observed and demonstrated by scanning electronic microscopy. Furthermore, filtration rate increases with either increasing cross-flow velocity or increasing filtration pressure.