Vapor injection heat pumps have been used to mitigate performance degradation under severe operating conditions. Low-global-warming-potential (GWP) refrigerants have been used to replace R134a in heat pumps to comply with F-gas regulations. However, experimental and optimization analyses of vapor-injection heat pumps with low-GWP refrigerants are limited in terms of injection conditions. In this study, the energy and environmental performance of vapor-injection heat pumps containing low-GWP refrigerants were experimentally investigated under various injection conditions. The capacity and coefficient of performance (COP) of the vapor-injection heat pumps using R152a and R1234yf were optimized and compared to those using R134a under various injection conditions. The optimized vapor-injection heat pump using R152a increased the heating and cooling COPs by 5.7% and 1.3%, respectively, compared to those using R134a because of its lower power consumption. In addition, the life-cycle climate performance (LCCP) of the optimized vapor-injection heat pumps using R152a and R1234yf were 4.7% lower and 3.0% higher, respectively, than those using R134a under practical conditions. Overall, R152a is recommended as a preferred alternative for vapor-injection heat pumps because of its high COP and low LCCP.