Effective mixing is vitally important to many microfluidic devices with applications in the areas of biotechnical industries, analytic chemistry and medical industries. In practice, passive micromixers are dependent on the proper layout of channel geometric configurations with obstacles deposited in microchannels to break-up and recombine the flow and reduce the diffusion path to improve the mixing performance. This study aims to investigate the mixing behavior of two different fluids in a passive micromixer with protruded boundary structures. The predicted mixing indexes at different longitudinal locations and Reynolds numbers achieved a good approximation of the experimental data in the literature for numerical simulations. The simulation results also indicated that intense vortices and secondary flows in spanwise planes were induced near the boundary protrusion regions to augment mixing efficiency along the flow course. In order to attain the optimal micromixer design, numerical calculations were attempted for the first time to thoroughly examine the effects of shape, length, width and placement of boundary protrusion structures on the mixing efficiency of a diamond-obstacles inserted micromixer.