This study examined the effect of build orientation on the surface finish of micro-optofludic (MoF) devices fabricated via a polydimethylsiloxane (PDMS)-based 3D-printing primary-secondary fabrication protocol, where an inkjet 3D-printing technique was implemented. The molds (i.e., primaries) for fabricating the MoF devices were 3D-printed in two orientations: along XY () and across YX () the printhead direction. Next, the surface finish was characterized using a profilometer to acquire the primary profile of the surface along the microchannel's edge. The results indicated that the build orientation had a strong influence on the latter, since displayed a tall and narrow Gaussian distribution for a channel width of 398.43 ± 0.29 µm; presented a slightly lower value of 393.74 ± 1.67 µm, characterized by a flat and broader distribution, highlighting greater variability due to more disruptive, orthogonally oriented, and striated patterns. These results were also confirmed by hydrodynamically testing the two MoF devices with an air-water slug flow process. A large experimental study was conducted by analyzing the mean period trend in the slug flow with respect to the imposed flow rate and build orientation. showed greater sensitivity to flow rate changes, attributed to its smoother, more consistent microchannel geometry. The slightly narrower average channel width in contributed to increased flow velocity at the expense of having worse discrimination capability at different flow rates. This study is relevant for optimizing 3D-printing strategies for the fabrication of high-performance microfluidic devices, where precise flow control is essential for applications in biomedical engineering, chemical processing, and lab-on-a-chip systems. These findings highlight the effect of microchannel morphology in tuning a system's sensitivity to flow rate modulation.