R600a/R601a mixtures are promising to be widely used in organic Rankine cycle (ORC) systems and also can promote the popularization of ORC technology. While, most of existing studies on ORC systems using R600a/R601a mixtures are based on certain heat source temperatures (generally below 150 degrees C) and saturated vapor at the evaporator outlet. Variations in the optimal mixture composition and superheat degree of R600a/R601a mixtures with increasing heat source temperature remain indeterminate thus far, especially for heat sources above 150 degrees C. Suitable approaches to further improve the system thermodynamic performance are also unclear. This study carried out a systematized analysis for subcritical ORC systems using R600a/R601a mixtures driven by heat sources of 100 degrees C to 200 degrees C, based on the first and second law analysis methods. Guidelines for selections of optimal mixture composition and cycle parameters were provided. Characteristics of exergy loss distribution were revealed to point out the crucial process to further improve the system thermodynamic performance. Results show that the effects of critical parameters on the selections of optimal mixture composition and evaporation pressure become remarkable for heat sources above approximately 160 degrees C. A minimum superheat degree is optimal for heat sources below 170 degrees C, whereas the optimal superheat degree may increase with increasing heat source temperature and R600a mass fraction for heat sources above 170 degrees C. Moreover, reducing the exergy losses in the heat absorption process, turbine, and condenser is vital to further increase the heat-work conversion efficiency for heat sources of approximately 100 degrees C to 160 degrees C, 170 degrees C to 190 degrees C, and 200 degrees C, respectively.