This paper experimentally investigates the effects of microhole eccentricity on the slip lengths of Stokes flow in microchannels with the bottom wall made of microhole arrays. The wettability of such microhole structures fabricated by the replica molding of polydimethylsiloxane is first analyzed measuring both static and dynamic contact angles. Subsequently, the drag reduction performance of the microchannels with such hydrophobic microhole surfaces is evaluated. The results indicate that the impact of microhole eccentricity on drag reduction performance correlates well with the contact angle hysteresis rather than with the static contact angle. Furthermore, microhole arrays with large normalized width and zero eccentricity show the minimum contact angle hysteresis of 18.7°. In these microchannels, the maximum percentage increase in the relative velocity is 39% corresponding to a slip length of 2.49 μm. For the same normalized width, increasing the normalized eccentricity to 2.6 increases the contact angle hysteresis to 36.5° that eventually reduces the percentage increase in relative velocity and slip length down to 16% and 0.91 μm, respectively. The obtained results are in qualitative agreement with the existing theoretical and numerical models. These findings provide additional insights in the design and fabrication of efficient micropatterned channels for reducing the flow resistance, and leave open questions for theoreticians to further investigate in this field.