Background Pressure-volume loops (PVL) provide vital information regarding ventricular performance and pathophysiology in cardiac disease. Unfortunately, acquisition of PVL by conductance technology is not feasible in neonates and small children due to the available human catheter size and resulting invasiveness. The aim of the study was to validate the accuracy of PVL in small hearts using volume data obtained by real-time three-dimensional echocardiography (3DE) and simultaneously acquired pressure data. Methods In 17 piglets (weight range: 3.6-8.0 kg) left ventricular PVL were generated by 3DE and simultaneous recordings of ventricular pressure using a mini pressure wire (PVL.sub.3D). PVL.sub.3D were compared to conductance catheter measurements (PVL.sub.Cond) under various hemodynamic conditions (baseline, alpha-adrenergic stimulation with phenylephrine, beta-adrenoreceptor-blockage using esmolol). In order to validate the accuracy of 3D volumetric data, cardiac magnetic resonance imaging (CMR) was performed in another 8 piglets. Results Correlation between CMR- and 3DE-derived volumes was good (enddiastolic volume: mean bias -0.03ml ±1.34ml). Computation of PVL.sub.3D in small hearts was feasible and comparable to results obtained by conductance technology. Bland-Altman analysis showed a low bias between PVL.sub.3D and PVL.sub.Cond. Systolic and diastolic parameters were closely associated (Intraclass-Correlation Coefficient for: systolic myocardial elastance 0.95, arterial elastance 0.93, diastolic relaxation constant tau 0.90, indexed end-diastolic volume 0.98). Hemodynamic changes under different conditions were well detected by both methods (ICC 0.82 to 0.98). Inter- and intra-observer coefficients of variation were below 5% for all parameters. Conclusions PVL.sub.3D generated from 3DE combined with mini pressure wire represent a novel, feasible and reliable method to assess different hemodynamic conditions of cardiac function in hearts comparable to neonate and infant size. This methodology may be integrated into clinical practice and cardiac catheterization programs and has the capability to contribute to clinical decision making even in small hearts.