<p>The efficiency of heat pumps strongly depends on the refrigerant. Hydrocarbons such as propane are established in many applications. In addition to pure fluids, zeotropic mixtures offer the potential to increase efficiency by minimizing losses during heat transfer due to the temperature glide. However, zeotropic mixtures are more sensitive to changes in external boundary conditions (temperature and temperature spread), which can lead to a&#xa0;reduced potential. Thus, this paper investigates both the improvement potential and the sensitivity with respect to operating conditions.</p><p>The investigation uses the mixture pair propane/isobutane. We analyze 21&#xa0;compositions, which are subsequently investigated in the refrigerant cycle with internal heat exchanger. The modeling includes a&#xa0;semi-physical compressor model, which allows the calculation of operating point and refrigerant dependent efficiencies.</p><p>The zeotropic mixture propane/isobutane (80/20) increases the <i>SCOP</i> for a&#xa0;supply temperature of 35 °C compared to pure propane by up to 6.4%, with a&#xa0;14.1% decrease in volumetric heating capacity. Increasing the supply temperature to 55 °C reduces the efficiency improvements to 4%, while the optimum composition remains. The highest influence on the optimum is the temperature spread of the secondary fluids. Reducing the heat source spread from 5–3 K shifts the optimal composition to 90 mol% propane. Analysis of the effects of the decomposition due to leakage shows direct influences on efficiency are negligible, with a&#xa0;decrease in efficiency of 1%. Overall, the studies demonstrate the potential of the zeotropic mixture propane/isobutane (80/20) despite its increased sensitivity to external influences.</p>