This study evaluated the feasibility of noninvasive intracardiac pressure estimation using subharmonic signals from ultrasound contrast agents in humans. This IRB approved proof-of-concept study included 15 consenting patients scheduled for left and right heart catheterization. During the catheterization procedure, Definity (Lantheus Medical Imaging, N Billerica, MA) was infused intravenously at 4–10 ml/min. Ultrasound scanning was performed with a Sonix RP (BK Ultrasound, Richmond, Canada) using pulse inversion, three incident acoustic output levels, and 2.5 MHz transmit frequency. Radiofrequency data were processed and subharmonic amplitudes were compared with the pressure catheter data. Correlation coefficient between subharmonic signals and pressure catheter data ranged from −0.3 to −0.9. For acquisitions with optimum acoustic output, pressure errors between the subharmonic technique and catheter were as low as 2.6 mmHg. However, automatically determining optimum acoustic output during scanning for each patient remains to be addressed before clinical applicability can be decided.