Environmental concerns are forcing the replacement of commonly used refrigerants, and finding new fluids is a top priority. Soon the R134a will be banned, and the hydro-fluoro-olefin (HFO) R1234ze(E) has been indicated as an alternative due to its smaller global warming potential (GWP) and shorter atmospheric lifetime. Nevertheless, for an optimal replacement, its thermo-fluid-dynamic characteristics have to be assessed. Flow boiling experiments (saturation temperature T_sat = 5 °C, mass flux G = 65 ÷ 222 kg·m⁻²·s⁻¹, mean quality x_m = 0.15 ÷ 0.95, quality changes ∆x = 0.06 ÷ 0.6) inside a microfin tube were performed to compare the pressure drop per unit length and the heat transfer coefficient provided by the two fluids. The results were benchmarked for some correlations. In commonly adopted operating conditions, the two fluids show a very similar behavior, while benchmark showed that some correlations are available to properly predict the pressure drop for both fluids. However, only one is satisfactory for the heat transfer coefficient. In conclusion, R1234ze(E) proved to be a suitable drop-in replacement for the R134a, whereas further efforts are recommended to refine and adapt the available predictive models.