In this study, the transport and deposition of colloidal particles onto a patterned membrane surface are analyzed by both numerical simulation and experiment. The channel Reynolds number (Re) and the size ratio of the particle to the pattern (a/h) are chosen as the major simulation parameters. With an increase in Re and a/h, the number of deposited particles decreases and the rate of permeate flux decline is reduced. Under certain specific combinations of the design parameters, the suspended particles are impeded to access the patterned membrane surface. Based on the particle trajectory analysis, it is claimed that "inaccessible zones", where the suspended particles cannot be accessed by the flow, are formed near the patterned membrane surface, with the increase in Re and a/h. Cross-flow microfiltration experiments using a poly(methyl methacrylate) (PMMA) particle suspension are also conducted to verify the trend in particle deposition observed in simulation. As the radius of the PMMA particle increases, the number of deposited particles is reduced and the critical flux for the onset of the particle deposition is increased, which qualitatively matches well with simulation. It is found that a patterned membrane can reduce tremendous amounts of colloidal fouling by prohibiting the access of the suspended particles to the membrane surface with the appropriate choice of design parameters such as Re and a/h.