Key Points  Through this analysis, CDC sought to identify U.S. counties where persons who inject drugs (PWID) appear especially vulnerable to the rapid spread of HIV or Hepatitis C infection, if introduced into this population.  Vulnerability does not mean inevitability or that there is a problem now.  The entire populace is not at risk; this analysis studies risk among PWID. Results show within the identified areas there are people that due to injection drug use (IDU) are considered highly vulnerable to the rapid spread of HIV/HCV, if introduced.  CDC identified 220 most vulnerable counties (top 5%) clustered as follows: o Appalachian Region o Northern New England o Ozarks Region o Northern part of the Michigan’s lower peninsula o In the Western region of the US there were a few states with one or two counties, but these did not cluster heavily in regions. Three recommendations are highlighted based on CDC’s assessment: 1. Assess for evidence of risk (i.e., evidence of injection drug use) using CDC’s analysis as the starting point and examining local data that is likely very informative; 2. Increase sensitivity to detect a potential outbreak by ensuring entities likely to encounter PWID (e.g., substance abuse treatment facilities, jails/prisons, emergency departments) offer HIV and HCV testing ; and 3. Prepare an outbreak response action plan, if indicated.