Several theoretical studies have predicted that refrigerant mixtures with glides of more than 20 K can yield COP improvements in heat pumps for operating conditions where the temperature difference between the heat source and heat sink is large, but experimental validations and quantifications are scarce. The application of high-glide mixtures (>20 K) in industrial heat pumps in the field is, therefore, still hampered by concerns about the behavior and handling of the mixtures. This study experimentally investigates hydrocarbon (HC) mixtures R-290/600 (propane/butane) and R-290/601 (propane/pentane) and compares them to previously tested mixtures of synthetic refrigerants. Comprehensive evaluations are presented regarding COP, compressor performance, pressure drop, heat transfer, and the possibility of inline composition determination. The mixtures were tested over a range of compositions at a source inlet temperature of 60 °C and a sink outlet temperature of 100 °C, with the heat sink and heat source temperature differences controlled to 35 K. R-290/601 at a mass composition of 70%/30% was found as the best mixture with a COP improvement of 19% over R-600 as the best pure fluid. The overall isentropic compressor efficiency was similar for HC and synthetic refrigerants, given equal suction and discharge pressures. Pressure drops in heat exchangers and connecting lines were equal for synthetic and HC mixtures at equal mass flow rates. This allows higher heating capacities of HC mixtures at a given pressure drop (mass flow rate) due to their wider vapor dome. A previously developed evaporator heat transfer correlation for synthetic refrigerant mixtures was applicable to the HC mixtures. A condenser heat transfer correlation previously fitted for synthetic refrigerants performed significantly worse for HC mixtures. Composition determination during operation and without sampling was possible with a deviation of at most 0.05 mass fraction using simple temperature and pressure measurements and REFPROP for thermodynamic property calculations. Overall, high-glide HC mixtures, just like mixtures of synthetic refrigerants, showed significant COP improvements for specific operating conditions despite a decreased heat transfer coefficient. Potential problems like composition shift or poor compressor performance were not encountered. As a next step, testing high-glide mixtures in pilot-plant installations is recommended.