Pressure measurements within the portal vein are clinically useful, but are currently estimated by the hepatic vein pressure gradient (HVPG), in which the pressure gradient is measured invasively using a wire pressure catheter. Alternatively, a noninvasive technique using subharmonic aided pressure estimation (SHAPE) may be useful for monitoring portal hypertension in patients. Portal pressure data was collected from 37 consenting patients undergoing transjugular liver biopsy as part of their clinical care. Within two hours post biopsy, patients received an infusion of Sonazoid (0.72 μL microbubbles/kg/hour; GE Healthcare, Oslo, Norway) and saline (120 ml/hour). Five minutes into the infusion, subjects were scanned with a modified Logiq9 ultrasound scanner (GE Healthcare, Milwaukee, WI) with a 4C curvilinear probe. After determining the optimal acoustic pressure, radio frequency (RF) data was obtained from the portal and hepatic veins for 5 seconds in triplicate. Patients with a subharmonic gradient of less than -4 dB were removed, since such values correspond to physiological impossible pressure levels (attributed to a lack of contrast within the hepatic vein). Subharmonic gradients were compared to the corresponding patient's HVPG obtained during biopsy. The subharmonic gradient was in good overall agreement with the patients' HVPG (R=0.86). Patients normally requiring clinical intervention (HVPG > 12 mmHg) showed significantly higher subharmonic gradient between the two veins (1.93±1.49 vs. -1.42±1.55 dB, p=0.0001, for patients requiring intervention vs. those that did not), indicating that SHAPE may be a useful tool for the diagnosis of portal hypertension. Finally, the subharmonic gradient was in very strong agreement with HVPG measurements amongst the subpopulation requiring intervention (R=0.97), indicating that SHAPE may also be a good monitor of treatment response in patients with portal hypertension, albeit in a limited sample size.