With the rapid development of large data center, the required power consumption increases sharply. The thermal management of that accounts for about 33% of energy consumption. Single phase liquid convection heat transfer of microchannel heat sink has been thought as one of the most promising methods. For energy efficient cooling, optimized microchannel structures is one important approach. Hence, the novel offset zigzag microchannnel is proposed and optimized for inlet Reynolds number ranging from 200–800 in this paper. The heat sink is composed of 30 parallel channels, and basic structure parameters of rectangular channel are width of 0.1mm, depth of 0.3mm, length of 5mm and pitch of 0.2mm. The numerical model considers entrance effect, viscous heating and the temperature-dependent thermal-physical properties. In order to study the influence of geometry on flow and heat transfer characteristics, two non-dimensional variables are defined, such as the length ratio of zigzag length to channel length (α) and the length ratio of zigzag expansion to zigzag length (γ). Results indicate the zigzag channel can effectively prevent the rise of heat surface temperature along the flow direction and increase the minimum temperature, which improves the temperature distribution uniformity. Under Rein=650 and α=0.04, the minimum temperature increases from 309.9K to 310.1K and maximum temperature decreases from 324.02K to 318.91K. For 0.04⩽α<0.1 and α<0.04 of Rein<500, the thermal characteristic is enhanced and the flow resistance also is reduced. Compared with rectangle channel, the maximum temperature and pressure drop of zigzag channel with α=0.04 of Rein=650 are also reduced from 324.02K to 318.76K and 29.81kPa to 26.75kPa, respectively. It can be interpreted that with the decrease of α, the porosity and convection heat transfer areas are increased and turbulence intensity of fluid flow is enhanced. The smaller γ is more favorable for the enhancement of heat transfer except for γ=0 due to the fluid stagnation at the bottom of zigzag cavity. However, compared with rectangular microchannel, heat transfer is enhanced for all cases and flow resistance is decreased besides γ=0.1 of Rein>500. For γ=0 of Rein=650, the maximum temperature and pressure drop are reduced from 324.02K to 318.01K and 298.81kPa to 27.91kPa, respectively. The overall thermal performance is measured with total thermal resistance vs pumping power. The best performance of offset zigzag microchannel is found at α=0.04 and γ=0.1. For Rein=800, the maximum temperature of heat surface is decreased 5.65K, the minimum increased 0.36K, and pumping power is decreased 1.4%. And thermal resistance is reduced by 17.4% at the Pp=0.167W.