Hemodynamically unstable patients supported by an extracorporeal life support (ECLS) circuit often receive additional support by intra-aortic balloon pump (IABP). However, it is not established whether support of the failing heart is improved by adjunctive IABP in both peripheral cannulation (PC) and central cannulation (CC) settings. Seven sheep were supported by an IABP and an ECLS system which were cannulated centrally as well as peripherally. In each cannulation configuration, hemodynamic and cardiac function indices were measured at baseline, ECLS, and ECLS plus IABP. The primary variables were mean coronary artery flow (Qcor), diastolic pressure time index (DPTI), left ventricular (LV) pressure-volume area (PVA), and tension time index (TTI). Additional IABP with ECLS support (CC/PC) decreased LV afterload (LV systolic peak pressure -4%, P<0.05/-8%, P<0.02), as well as TTI -2%/-10% and PVA -10%/-12% (P<0.03). Coronary perfusion was increased by additional IABP: CC, Qcor, +9%, and DPTI, +18% (P<0.02); PC, Qcor,+6%, and DPTI, +11% (P<0.05). IABP augmented the myocardial oxygen supply/demand ratios (CC/PC): Qcor/(PVA.heart rate) (+21%/+22%, P<0.02) and DPTI/TTI (+27%/+24%, P<0.03). In case of low arterial pressure (<50 mm Hg) and reduced ECLS flow, the overall hemodynamic profile improved only with central cannulation. We conclude that in both central and peripheral ECLS cannulation settings, adjunctive IABP improves the myocardial oxygen supply demand balance. In case of low cardiac output and insufficient extracorporeal flow with PC, adjunctive IABP may be contraindicated.