The Up-THERM heat converter is an unsteady, two-phase thermofluidic oscillator that employs an organic working fluid, which is currently being considered as a prime-mover in small- to medium-scale combined heat and power (CHP) applications. In this paper, the Up-THERM heat converter is compared to a basic (sub-critical, non-regenerative) organic Rankine cycle (ORC) heat engine with respect to their power outputs, thermal efficiencies and exergy efficiencies, as well as their capital and specific costs. The study focuses on a pre-specified Up-THERM design in a selected application, a heat-source temperature range from 210 °C to 500 °C and five different working fluids (three n-alkanes and two refrigerants). A modeling methodology is developed that allows the above thermo-economic performance indicators to be estimated for the two power-generation systems. For the chosen applications, the power output of the ORC engine is generally higher than that of the Up-THERM heat converter. However, the capital costs of the Up-THERM heat converter are lower than those of the ORC engine. Although the specific costs (£/kW) of the ORC engine are lower than those of the Up-THERM converter at low heat-source temperatures, the two systems become progressively comparable at higher temperatures, with the Up-THERM heat converter attaining a considerably lower specific cost at the highest heat-source temperatures considered.