R134a is ongoing a phase-down process in several countries and R1234yf can be a viable low GWP alternative together with R1234ze(E). Since new experimental data are always requested by researchers and industry to increase the global database, to assess the existing correlations, and to expand the knowledge about the refrigerant applications, in this paper more than 100 new heat transfer coefficient and frictional pressure drop data are presented during R1234yf flow boiling inside a 4 mm inner diameter smooth copper tube. Three saturation temperatures 10 °C, 15 °C and 20 °C were investigated and critically discussed, for each temperature the heat flux ranged from 15 to 30 kW m−2 and the mass velocity from 300 to 600 kg m−2 s−1. Furthermore, some literature correlations were implemented and carefully examined and their deviations are reported. Finally, the R1234yf heat transfer performance is compared against R1234ze(E) and R134a, highlighting the peculiarities of each alternative molecule. R1234ze(E) outperforms the other refrigerants at high vapor qualities but both R1234yf and R1234ze(E) can be viable low GWP substitutes to R134a, if the new design is able to take advantage of the qualities of each refrigerant.