To investigate the feasibility of ultrasonic recanalization of obstructed human coronary arteries in vitro, high-intensity ultrasound was applied to 16 coronary arteries obtained at autopsy, using a prototype instrument enabling insonification through a catheter tip. It was a 119 cm long, 0.95 mm thick wire in an 8Fr catheter connected to an external ultrasonic transformer and power generator. A 5 MHz phased-array 2-dimensional echocardiography instrument was used to determine minimal luminal diameter and percent diameter narrowing before and after ultrasound application. The ultrasonic energy was delivered at 21.5 kHz and with a 52 ± 19 μmm average amplitude of tip displacement. The mean percent luminal diameter narrowing, flow rate and mean pressure gradient before ultrasound exposure were 74 ± 11%, 97 ± 61 ml/min, and 92 ± 18 mm Hg, respectively. After recanalization, the mean percent luminal diameter narrowing decreased to 45 ± 17% (p < 0.001), the mean flow rate increased to 84 ± 92 ml/min (p < 0.001), and the mean pressure gradient was reduced to 45 ± 24 mm Hg (p < 0.001). Of the debris particles, 95% had a diameter <9 μm (range 5 to 12). Arterial perforation occurred in 5 of 16 arteries (31%) and all 5 occurred due to stiff wire manipulation and without ultrasound application. Mechanical fracture of the wire occurred in 8 cases (50%). No signs of thermal injury were found on histology. Thus, ultrasonic recanalization of human coronary arteries in vitro is feasible. It may reduce obstruction and improve blood flow. Debris sizes are sufficiently small to minimize the hazard of peripheral embolization.