This paper presents the increase of the overall reaction rate of a heterogeneously catalyzed multi-phase reaction using a carbon nanofiber (CNF) based catalyst with a factor of 3.5–4 compared with an unsupported flat plate catalyst in a microreactor. This was done by quantifying the hydrogen reaction rates for three different CNF layers with different layer and fiber thicknesses and permeability attached to a microchannel wall at different flow regimes and comparing them with the reaction rate of an unsupported flat plate catalyst. The CNF layer with the most open structure and the largest CNF layer thickness shows an increase of the overall reaction rate with a factor of approximately 3.5–4 in comparison with the unsupported flat plate catalyst, whilst keeping the selectivity towards the intermediate product over 95%. Furthermore, the influence of the CNF layers on the gas hold-up and the flow regimes were investigated. The gas hold-up is linearly dependent on the relative gas velocity according to the Armand correlation for all the tested CNF layers. The CNF layers do not influence the flow patterns, and the Taylor/slug, slug/ring, ring and annular flow regimes are observed for all CNF layers.