Power pulse inversion (PPI) has been developed for echocontrast specific imaging in order to reduce destruction of microbubbles. The purpose of this study was to evaluate PPI for real-time contrast echocardiography. Therefore, in vitro studies in a physiological flow-phantom and clinical examinations in patients with coronary artery disease were performed. The in vitro rersults of this study indicate that PPI allows real-time imaging at low emission power and is almost nondestructive to contrast microbubbles of Definity. At this low emission power a strong linear relationship between the dosage of the contrast agent and the resulting PPI signal intensity was found (R = 0.998, p < 0.001). In the clinical examinations real-time imaging using low mechanical index PPI resulted in strong myocardial signals and a complete filling of the cavities indicating absence of bubble destruction. Most striking was the ability of PPI to display myocardial thickening and wall motion simultaneously with the assessment of myocardial contrast replenishment following ultrasound induced bubble destruction by high power frames. We conclude that PPI allows nondestructive contrast imaging both in experimental and clinical settings. Therefore, real-time imaging of myocardial perfusion and real-time assessment of contrast replenishment following ultrasound induced destruction of microbubbles is feasible. Moreover, PPI allows simultaneous assessment of perfusion and myocardial function.