A medical device known as an implantable therapeutic substance infusion device is configured for implanting in humans to deliver a therapeutic substance such as pharmaceutical compositions, genetic materials, and biologics to treat a variety of medical conditions such as pain, spastisity, cancer, and many other conditions. The therapeutic substance infusion device has a piston pump with an anti-cavitation valve to reduce gas formation, increase accuracy, improve efficiency and has many other improvements. The therapeutic substance infusion device has a housing, a therapeutic substance reservoir, a power source carried in the housing, electronics, a piston pump, an inlet valve, and anti-cavitation valve. The piston pump is configured for pumping therapeutic substance from the therapeutic substance reservoir through an infusion port at a programmed rate. The anti-cavitation is in fluid communication with a reservoir outlet and an inlet chamber to substantially preventing retrograde flow of therapeutic substance from the inlet chamber back through the reservoir outlet. Many embodiments of the anti-cavitation valve and its methods of operation are possible.