A numerical study has been carried out to investigate heat transfer enhancement in channel flow using large-scale vortices. A square cylinder, inclined with respect to the main flow direction, is located at the center of the channel flow, generating a separation region and Karman vortices. Two cases are considered; one with a fixed blockage ratio and the other one with a fixed cylinder size. In both cases, the flow characteristics downstream of the cylinder significantly change depending on the inclination angle. As a result, heat transfer from channel wall is significantly enhanced due to increased vertical-velocity fluctuations induced by the large-scale vortices shed from the cylinder. Quantitative results as well as qualitative physical explanation are presented to justify the effectiveness of the inclined square cylinder as a vortex generator to enhance heat transfer from channel wall.