The present contribution reports the outcome of an experimental and numerical investigation of the behavior of a constant-temperature hot-wire anemometer in the high-subsonic flow up to a Mach number of 0.7 of the organic vapor Novec™ 649 at pressure and temperature levels of typical organic Rankine cycle (ORC) turbine applications. The experiments were carried out in the calibration section of a closed-loop organic vapor wind tunnel test facility enabling the independent variation of Reynolds numbers, Mach numbers, and total temperature within a certain range. It was found that the calibration and the determination of the sensitivity coefficients can be done in a way as proposed by de Souza and Tavoularis for air. The sensitivity coefficients for velocity and density were essentially equal for higher overheat ratios which support the interpretation of the signals and data reduction for turbulent quantities. Computational fluid dynamics (CFD) provided additional insight into potential real gas effects for hot-wire performance.