The effect of structured roughness on the heat transfer of water flowing through minichannels was experimentally investigated in this study. The test channels were formed by two 12.7 mm wide × 94.6 mm long stainless steel strips. Eight structured roughness elements were generated using a wire electrical discharge machining (EDM) process as lateral grooves of sinusoidal profile on the channel walls. The height of the roughness structures ranged from 18 μm to 96 μm, and the pitch was varied from 250 μm to 400 μm. The hydraulic diameter of the rectangular flow channels ranged from 0.71 mm to 1.87 mm, while the constricted hydraulic diameter (obtained by using the narrowest flow gap) ranged from 0.68 mm to 1.76 mm. After accounting for heat losses from the edges and end sections, the heat transfer coefficient for smooth channels was found to be in good agreement with the conventional correlations in the laminar entry region as well as in the laminar fully developed region. All roughness elements were found to enhance the heat transfer. In the ranges of parameters tested, the roughness element pitch was found to have almost no effect, while the heat transfer coefficient was significantly enhanced by increasing the roughness element height. An earlier transition from laminar to turbulent flow was observed with increasing relative roughness (ratio of roughness height to hydraulic diameter). For the roughness element designated as B-1 with a pitch of 250 μm, roughness height of 96 μm and a constricted hydraulic diameter of 690 μm, a maximum heat transfer enhancement of 377% was obtained, while the corresponding friction factor increase was 371% in the laminar fully developed region. Comparing different enhancement techniques reported in the literature, the highest roughness element tested in the present work resulted in the highest thermal performance factor, defined as the ratio of heat transfer enhancement factor (over smooth channels) and the corresponding friction enhancement factor to the power 1/3.