Various 1D simulation tools (KULI & LMS Amesim) and 3D simulation tools (ANSYS FLUENT®) can be used to size and evaluate truck cooling system design. In this paper, ANSYS FLUENT is used to analyze and validate the design of medium duty truck cooling systems. LMS Amesim is used to verify the quality of heat exchanger input data.This paper discusses design and simulation of parent and derivative trucks. As a first step, the parent truck was modeled in FLUENT (using standard' k - ε model) with detailed fan and underhood geometry. The fan is modeled using Multiple Reference Frame (MRF) method. Detailed geometry of heat exchangers is skipped. The heat exchangers are represented by regular shape cell zones with porous medium and dual cell heat exchanger models to account for their contributions to the entire system in both flow and temperature distribution. Good agreement is observed between numerical and experimental engine out temperatures at different engine operating conditions. Once the CFD approach is validated, CFD simulation is carried out with derivative truck design. The rich information from CFD simulations will be used to evaluate the new designs much faster and eventually improve the efficiency of cooling system designs. Implemented design recommendations are shown to meet the cooling requirements.