With the advancement of additive manufacturing techniques, manifold-microchannel heat exchanger has proved its fabrication feasibility and performance advantage compared to the conventional heat exchanger used on aircraft system. However, a fully-featured manifold-microchannel heat exchanger is typically too detailed to model and perform CFD on considering the number of microchannels within the heat exchanger design. However, microchannels have been shown to be reasonably approximated by a porous medium with specific calibrated resistances in each flow direction. To reduce the computational complexity, a porous medium approach is presented in this study to predict the pressure drop for several manifold-microchannel heat exchangers with different microchannel numbers. In order to determine the effectiveness of this porous medium approach, a fully detailed model was created to mirror the experimental data. Once the manifold-microchannel pressure drop from the detailed model was found to be mesh-independent and accurate within 5%, a simplified model was created with a single porous medium zone where the microchannel fluid and solid had been. To confirm the independence of this porous medium approximation with respect to the number of microchannels, several models with differing numbers of microchannels, but otherwise identical microchannel dimensions and manifold shapes were created. It is found that the manifold-microchannel pressure drop prediction for each model demonstrated a match within 5% compared to the experimental data.