Computational fluid dynamics (CFD) is a powerful tool for analyzing the performance of heat exchangers. However, such an approach may be often limited by unaffordable computational time. In this paper, a multiscale CFD capable of accurately and efficiently prediction of the heat transfer of compact heat exchangers is presented. This methodology is based on a small-scale CFD analysis of a single tube and a small element of the compact heat exchanger, and it is able to predict the thermal performance of an entire heat exchanger in a wide range of inlet conditions, with a reduced computational time. The proposed up-scaling procedure makes use of specific approximations and correlations derived from the CFD model and literature, in order to consider the typical phenomena occurring in compact heat exchangers under laminar flow conditions. Results demonstrate an excellent accuracy when compared to experimental data (discrepancies <4.3%). This novel up-scaling method may have a strong impact on modeling and design strategy of compact heat exchangers in the industrial field.