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A non-invasive software upgrade method for permanent implantable medical devices was developed to alleviate patients' suffering due to malfunctions because of software faults, which may cause serious adverse health consequences or require enhancements with new software. The programs distributed to the internal implantable pulse generator (I PG) from the external programmer have been developed so that the upgrade service program in the IPG is simplified with most complex functions executed by the external programmer. A bidirectional protocol including frame definition and transmission mode was designed to insure secure upgrades. A neuro-stimulator was used to verify the upgrade solution with no additional elements, to maintain the hardware reliability. This study emphasizes how to insure a secure and stable upgrade process and reduce power consumption for special wireless and life safety-critical applications. Tests on rhesus monkeys to evaluate the feasibility of the approach for an I PG used for brain stimulation evaluation show that the software upgrade can be implemented stably with good tolerance to the wireless data transmissions.