The RII was created in 1991 with authorization from the University of Texas Board of Regents, the Texas Higher Education Coordinating Board (THECB) and the Texas State Legislature. Facilities funding was provided from a variety of philanthropic sources, with the Ross Perot Foundation making the largest donation ($10 million). The Department of Veterans Affairs and the Department of Defense jointly contributed funds for instrumentation. Operating funds were provided by a Special Project appropriation from the Texas State Legislature. After a successful performance review by the THECB, the RII was a made a permanent component of the UTHSCSA budget in 1996.

From its inception, the RII has been directed by Peter T. Fox, M.D.