A three-dimensional analysis procedure for the thermal performance of a manifold microchannel heat sink has been developed and applied to optimize the heat-sink design. The system of fully elliptic equations, that govern the flow and thermal fields, are solved by a SIMPLE-type finite volume method, while the optimal geometric shape is traced by a steepest descent technique. For a given pumping power, the optimal design variables that minimize the thermal resistance are obtained iteratively. The procedure is robust and the optimal state is reached within six global iterations. Comparing with the comparable traditional microchannel heat sink, the thermal resistance is reduced by more than a half while the temperature uniformity on the heated wall is improved by tenfold. The sensitivity of the thermal performance on each design variable is also examined and presented in the paper. Among various design variables, the channel width and depth are more crucial than others to the heat-sink performance. The optimal dimensions and corresponding thermal resistance have a power-law dependence on the pumping power.