This paper presents a numerical investigation of a single-phase manifold microchannel cooler (MMC) heat exchanger demonstrating a reduction in fluid pressure drop while improving chip-temperature uniformity. This modeling work includes the entire manifold length with multiple microchannels, whereas previous models have only focused on individual microchannels, ignoring complex manifold effects. Computational Fluid Dynamic (CFD) models were used to identify the impact of varying both the manifold and microchannel fin and channel dimensions, and a sensitivity analysis was performed with respect to system pressure drop, rise in device temperature, and thermal uniformity. This modeling work demonstrated both large velocity gradients between microchannels, as well as fluidic swirling in the microchannels that significantly improved the heat transfer coefficient. These results are absent from unit-cell type models. The results of the full MMC model showed significantly improved chip-temperature uniformity when large (approximately 10X) differences in velocity occurred between microchannels. The simulations also showed that, for equivalent thermal performance, the MMC design resulted in a 97% reduction in system pressure drop when compared to an equivalent straight microchannel cooler. Finally, the numerical pressure drop results were compared to a simpler, one-dimensional approximation based on the Hagen-Poiseuille equation. While under-predicting total pressure drop, the analytical equation does capture prevailing trends of the effects of channel dimensions on the pressure drop and can be used for rapid evaluation of numerous tradeoffs from a system perspective. Published by Elsevier Ltd.