Implantable mechanical left ventricular assist devices (LVADs) are used as a bridge or alternative to heart transplantation. Peroperative transesophageal echocardiography is commonly applied during implantation. Significant air embolism may occur as a result of air leakage at connections and anastomoses when LV filling becomes inadequate, and this must be prevented. Early suspicion and detection of air is mandatory to avoid negative circulatory effects. We hypothesized that monitoring of heart chamber size and occurrence of single air bubbles using second harmonic imaging (SHI) echocardiography may prevent risk for significant air embolism. After implantation of the LVAD in 10 calves, invasive hemodynamic monitoring and epicardial SHI were performed while increasing pump speed. Air bubbles in the ascending aorta were monitored and the left heart visualized for off-line dimensional analysis. Detection of air bubbles in the ascending aorta preceded their appearance in the left ventricle. They occurred exclusively but not always after a decrease in left atrial (LA) size. Decrease in LA pressure did not predict bubble detection or reduction in LA size. We conclude that SHI detects spontaneous ultrasound contrast during implantation of a LVAD and that a decrease in LA size is a warning that air embolism is imminent.