Levosimendan enhances cardiac contractility via Ca²⁺ sensitization and induces vasodilation through the activation of K_ATP/BK_Ca. However, the hemodynamic effects of levosimendan as well as its metabolites, OR-1896 and OR-1855, relative to plasma concentrations achieved are not well defined. Thus, levosimendan, OR-1896, OR-1855 or vehicle was infused at 0.01, 0.03, 0.1, and 0.3 µmol/kg/30min targeting therapeutic to supratherapeutic concentrations of total levosimendan (C_max=62 ng/mL). Results were compared to those of the 1-agonist, dobutamine, and the PDE3 inhibitor, milrinone. Peak concentrations of levosimendan, OR-1896, and OR-1855 were 455±21, 126±6, and 136±6 ng/mL. Levosimendan and OR-1896 produced dose-dependent reductions in MAP (-31±2 and -42±3 mmHg, respectively) and systemic resistance without affecting pulse-pressure (PP), effects paralleled by increases in heart rate; OR-1855 produced no effect at any dose tested. Dobutamine, but not milrinone, increased MAP and PP (17±2 and 23±2 mmHg). Regarding potency to elicit reductions in time-to-peak-pressure and time-to-systolic-pressure-recovery: OR-1896>levosimendan>milrinone>dobutamine. Levosimendan and OR-1896 elicited dose-dependent increases in dP/dt (118±10% and 133±13%) concomitant with reductions in LVEDP and ejection time. However, neither levosimendan nor OR-1896 produced increases in myocardial oxygen consumption at inotropic and vasodilatory concentrations whereas dobutamine increased myocardial oxygen consumption (79% above baseline). Effects of the levosimendan and OR-1896 were limited to the systemic circulation; neither compound produced changes in pulmonary pressure whereas dobutamine produced profound increases (74±13%). Thus, levosimendan and OR-1896 are hemodynamically active in the anesthetized dog at concentrations observed clinically and elicit cardiovascular effects consistent with activation of both K_ATP/BK_Ca and Ca²⁺ sensitization whereas OR-1855 is inactive on endpoints measured in this study.