Although the role of creatine in muscle metabolism is well understood, there is still uncertainty as to its effects at supplemented levels. With this in mind, this study was designed to investigate the direct effects of commercially available creatine on the isolated rat heart, retrogradely perfused and infused with varying concentrations of creatine (1.25, 2.5, 5 and 10 mM) to determine its effects on heart rate, coronary flow and ventricular pressure. Furthermore, tissue from these hearts was used to investigate the cardiotoxic potential of supplemented levels of creatine. Results indicate that creatine directly improves the functioning of the heart under normal conditions with respect to heart rate and ventricular pressure, but may be detrimental to the functioning of energy-deprived hearts. It also showed no cardiotoxic properties since it increased the baseline levels of adenosine triphosphate (ATP) and decreased the levels of isocitrate dehydrogenase (lCD), indicating a decrease in cellular death compared with non-supplemented control hearts.