The pressure drop in a microchannel Fischer-Tropsch reactor was investigated by means of a fluid dynamics model developed by the authors. The developed model takes into account roughness of the microchannel wall induced by catalyst particle deposition on the surface of the microchannel. The presented simulation procedure takes into account the variation of the synthesis product composition and the variation of thermal properties of the liquid and gas phases along the microchannel length as functions of pressure, temperature, conversion rate and chain growth coefficient. Liquid and gaseous products down flow are modeled in the annular flow approximation. The obtained results are presented for two general types of microchannels, i.e. for rough-walled and for smooth-walled microchannels. It is shown that fluid dynamics in rough-walled and smooth-walled microchannels are dramatically different. It is established that a mean critical diameter can be introduced. The microchannels with diameter below the mean critical value can experience operation difficulty due to by high aerodynamic resistance or can even become completely flooded.