BACKGROUND: Ventricular assist devices are gaining ground in the therapeutic treatment of chronic heart failure. These devices are sometimes used as a bridge to recovery by unloading the left ventricle (LV) and restoring its function. It is therefore important to preserve the heart muscle and apply less invasive implantation methods. METHODS: In this study ventricular unloading was achieved in 7 healthy sheep with a rotary blood pump at different pump flow levels. Ventricular cannulation via the left atrium (LA) and through the mitral valve was compared to atrial cannulation. The unloading of the heart was assessed with LV pressure-volume loops, derived energetic parameters, and an estimate of LV wall stress. RESULTS: No significant difference between the cannulations was found for any flow or pressure. LA cannulation, however, resulted in significantly lower stroke volumes and stroke work for all pump flow levels. Irrespective of cannulation site, LV volumes and energetic parameters showed a significant decrease with increasing pump flow. CONCLUSION: LV assist with a rotary blood pump can provide sufficient unloading with atrial cannulation.