The European directive 2006/40/CE, known as MAC directive, imposes a gradual dereliction of the fluorinated greenhouse gases having a Global Warming Potential (GWP) higher than 150 as refrigerant fluids in HVAC systems for mobile air-conditioning. The refrigerant fluid R134a, which is one of the most employed refrigerant fluids in mobile air-conditioning, belongs to this category of banned fluids. A widely accepted solution for complying the restrictions introduced by the MAC directive, is to use the refrigerant fluid HFO-1234yf (GWP = 4) in substitution to the HFC-134a (GWP = 1430). Even if in open literature the compatibility of the components of the HVAC system has been proved for the usage with both the fluids, it has been equally underlined that systems employing R1234yf as refrigerant fluid require slight modifications in order to achieve similar performances with systems using R134a as refrigerant fluid. This work focuses on the comparison of the HVAC system performances when the refrigerant fluid R1234yf is used as replacement of R134a. In particular, this paper deals with the optimization of the HVAC system in electric mobility, where the energy consumption due to the HVAC system is crucial on the state of charge of the batteries of the vehicle. The analysis of the system is performed in a Matlab-Simulink environment in which both the HVAC system and the vehicle cabin have been modeled. The Simulink model allows to analyze the HVAC system performances in a guide cycle. In this way, it is possible to compare the effect of the two refrigerant fluids on the system performances and to monitor either the comfort conditions inside the vehicle cabin as well as the state of charge of the batteries. The model developed allows to study the system optimization in order to decrease the batteries' energy consumption, keeping the comfort conditions inside the vehicle.