The aim of this study was to examine whether short- and long-term gene transfer of Ca²⁺ handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) (Banding+SERCA), parvalbumin (Banding+Parv) or β-galactosidase (Banding+βgal), or an adeno-associated virus carrying SERCA2a (Banding+AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. “Banding”, “Banding+βgal” and “Banding+saline” groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP_0.1), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP_0.1) and slower LV relaxation rate, compared with “Normal” and “Sham”. However, “Banding+SERCA” and “Banding+Parv” showed high ESP_0.1, low EDP_0.1 and fast LV relaxation rate. In “Banding”, “Banding+βgal” and “Banding+saline”, slope of relation between cardiac oxygen consumption and systolic pressure–volume area, O₂ cost of total mechanical energy, was twice higher than normal value, whereas slope in “Baning+SERCA” and “Banding+Parv” was similar to normal value. Furthermore, O₂ cost of LV contractility in the 3 control banding groups was ∼3 times higher than normal value, whereas O₂ cost of contractility in “Banding+SERCA”, “Banding+AAV.SERCA” and “Banding+Parv” was as low as normal value. Thus, high O₂ costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.