Polymer microspheres can deposit successively in microfluidic channels until they block a flow passage, which then leads to device failure. This article presents investigations of the effect of particle size distribution on the dynamics of channel blockage in microfluidic systems. The presented measurements and observations show that a low concentration of relatively large particles in a suspension has a major effect on the average time for a microchannel to be blocked by particles. Depending on the size distribution of particles in a suspension microchannel blockage occurs through successive particle deposition, particle size exclusion, or through a combination of these effects.