Background: Admittance catheter-derived pressure–volume (PV) analysis offers the ability to assess dynamic changes in ventricular performance. The present study was designed to evaluate the feasibility and accuracy of biventricular PV analysis by comparing admittance catheter-derived measurements of left (LV) and right ventricular (RV) volumes with data obtained from simultaneous contrast-enhanced cardiac multi-detector computed tomography (MDCT) before, during, and after transient pressure overload (TPO) in swine. Load-independent parameters of LV and RV systolic function were also assessed to determine whether each ventricle exhibits a similar susceptibility to mechanical stretch-induced myocardial stunning. Methods: Closed-chest propofol-anesthetized swine (n = 5) were instrumented with a Swan-Ganz catheter and admittance catheters in the LV and RV for continuous biventricular PV analysis (ADV500; Transonic Scisense, Inc., London, ON, Canada). Cardiac MDCT with iodinated contrast (1 ml/kg at 4 ml/s) was performed before, during, and 30 min after TPO elicited by a 1 h intravenous infusion of phenylephrine (PE; 300 µg/min). Right and left ventricular end-diastolic volume, end-systolic volume, and stroke volume were calculated simultaneously with each modality. Load-independent systolic function was derived from biventricular PV loops collected during inferior vena cava occlusion at baseline and 30 min after PE. Results: PE elicited a significant rise in LV pressure and RV pressure that normalized 30 min after the end of the infusion period. Biventricular PV analysis demonstrated a significant increase in LV and RV end-diastolic volume and end-systolic volume during PE that normalized in the RV, but not LV, 30 min after cessation of PE. These changes were confirmed by contrast-enhanced cardiac MDCT-derived measurement of ventricular volumes, with no significant differences between PV and MDCT at any timepoint. Persistent LV dilatation after PE was accompanied by a reduction in load-dependent (dP/dtmax) and load-independent (ESPVR and PRSW) parameters of LV systolic function, reflecting stretch-induced stunning following a ~6-fold rise in LV end-diastolic pressure during PE. This was not observed in the RV, as load-dependent and load-independent parameters of RV systolic function were preserved following PE-induced TPO. Conclusions: Biventricular PV analysis is feasible in swine and provides accurate continuous measurement of ventricular volumes compared with intermittent contrast-enhanced cardiac MDCT. Employing this approach during transient PE infusion demonstrated persistent chamber dilatation and systolic dysfunction in the LV, but not RV, consistent with stretch-induced stunning caused by an acute elevation in preload. The absence of stretch-induced stunning in the RV may be linked to inherent differences in compliance relative to the LV, as well as a diminished pressor response to PE in the pulmonary vs. systemic circulation. The data included in this manuscript were originally shared with the scientific community via two peer-reviewed abstracts referenced within.