This paper presents an experimental analysis of a vapor compression system using R1234yf as a drop-in replacement for R134a. In this work, we compare the energy performance of both refrigerants, R134a and R1234yf, in a monitored vapor compression system under a wide range of working conditions. So, the experimental tests are carried out varying the condensing temperature, the evaporating temperature, the superheating degree, the compressor speed, and the internal heat exchanger use. Comparisons are made taking refrigerant R134a as baseline, and the results show that the cooling capacity obtained with R1234yf in a R134a vapor compression system is about 9% lower than that obtained with R134a in the studied range. Also, when using R1234yf, the system shows values of COP about 19% lower than those obtained using R134a, being the minor difference for higher condensing temperatures. Finally, using an internal heat exchanger these differences in the energy performance are significantly reduced. ► We present an experimental analysis of R1234yf as a drop-in replacement for R134a. ► Comparisons are carried out using the energy performance parameters. ► Cooling capacity obtained using R1234yf is about 9% lower than that using R134a. ► Volumetric efficiency obtained using R1234yf is 5% lower than that using R134a. ► Similar energy performance obtained using an IHX with high condensing temperatures.