In August 2005, a health-care facility in Pennsylvania reported the occurrence of Ralstonia spp. in six patients aged 21 days to 8 years to the Philadelphia Department of Health and CDC. Preliminary laboratory and epidemiologic investigation identified the Vapotherm 2000i oxygen delivery device (Vapotherm Inc., Stevensville, Maryland) as an associated risk factor for recovery of the organism from blood and respiratory tract samples. Although the source of Ralstonia has not yet been identified, Vapotherm has created new infection-control procedures to reduce the risk for infectious disease transmission among patients using their machines. This report summarizes the initial results of this ongoing investigation and provides recommendations to prevent further spread of Ralstonia species in hospitals.