Aim: The purpose of this work is to develop an ultra-compact wearable pneumatic drive unit for ventricular assist device. Methods: The drive unit consists of a brushless DC motor, a crankshaft, a cylinder-piston, noncircular gears and air pressure regulation valves. The reciprocating motion of the cylinder-piston makes the air pressure which drives the blood pump. The noncircular gears make systolic ratio and the air pressure regulation valves regulate the maximum and minimum pressure in the cylinder-piston. The weight of the drive unit is approximately 1.7 kg. Results: The drive unit was tested in an overflow type circulation mock test using a Toyobo VAD blood pump of 70 mL of stroke volume. Pre-load and after-load were set at 10 mm Hg and 120 mm Hg, respectively. The maximum flow rate was 7 1/min at 100 bpm. The drive unit was also examined by an in vivo animal experiment. A Holstein calf weighing 80kg with the Toyobo VAD blood pump wore the drive unit on his back. The pumping rate and the systolic ratio were set at 80 bpm and 40%, respectively. The calf survived for more than 1 month in good general condition. The bypass flow was maintained 3-4 l/min. The electric power consumption of the drive unit was maintained at around 12 W. Conclusion: The performance of the ultra-compact wearable pneumatic drive unit was confirmed in vitro experiment and in vivo animal study. These results indicate that the developed drive unit has a potential to become a mechanical circulatory support system of the human heart.