Wave intensity analysis (WIA) is beginning to be applied to the coronary circulation both to better understand coronary physiology and as a diagnostic tool. Separation of wave intensity (WI) into forward and backward traveling components requires knowledge of pulse wave velocity at the point of measurement, which at present cannot accurately be determined in human coronary vessels. This prompted us to study the sensitivity of wave separation to variations in wave speed. An estimate of wave speed (SPc) was calculated based on measured distal intracoronary pressure and Doppler velocity in normal and diseased coronary vessels of patients during hyperemia. Changes of the area under separated WI waveforms were determined for a range of wave speeds from 25 to 200% of the calculated value. Variations in wave speed between half to twice the calculated value did not substantially alter separated WI. In conclusion, although SPc lacks accuracy in determining local coronary wave speed it is within limits still applicable for wave separation in coronary WIA.