In this study, the authors experimentally investigate the performance of the organic Rankine cycle (ORC) and screw expander under the influence of supply pressure and pressure ratio over the expander. Three tests were performed with expander pressure ratios of 2.4–3.5, 3.0–4.6, and 3.3–6.1, which cover the over-expansion and under-expansion operating modes. The test results show a maximum expander isentropic efficiency of 72.4% and a relative cycle efficiency of 10.5% at an evaporation temperature of 101 °C and condensation temperature of 45 °C. At a given pressure ratio over the expander, a higher supply pressure to the expander causes a higher expander isentropic efficiency and higher cycle efficiency in the over-expansion mode. However, in the under-expansion mode, the higher supply pressure results in a lower expander isentropic efficiency and adversely affects the cycle efficiency. The results also show that under the condition of operation at a given pressure ratio, a higher supply pressure yields a larger power output owing to the increased mass flow rate at the higher supply pressure. The study results demonstrate that a screw-expander ORC can be operated with a wide range of heat sources and heat sinks with satisfactory cycle efficiency.