Persons who inject drugs (PWID) shoulder the greater part of the hepatitis C virus (HCV) epidemic in the USA. PWID are also disproportionately affected by limited access to health care and preventative services. We sought to compare current health care coverage, HCV, and HIV testing history, hepatitis A and B vaccination coverage, and co-occurring substance use among PWID in two US cities with similar estimated numbers of PWID. Using data from the 2009 National HIV Behavioral Surveillance system in Denver (n = 428) and Seattle (n = 507), we compared HCV seroprevalence and health care needs among PWID. Overall, 73 % of participants who tested for HCV antibody were positive. Among those who were HCV antibody-positive, vaccination coverage for hepatitis A and B was low (43 % in Denver and 34 % in Seattle) and did not differ significantly from those who were antibody-negative. Similarly, participation in alcohol or drug treatment programs during the preceding 12 months was not significantly higher among those who were HCV antibody-positive in either city. Significantly fewer participants in Denver had health care coverage compared to Seattle participants (45 vs. 67 %, p < 0.001). However, more participants in Seattle reported being disabled for work and, thus, more likely to be receiving health care coverage through the federal Medicaid program. In both cities, the vast majority of those who were aware of their HCV infection reported not receiving treatment (90 % in Denver and 86 % in Seattle). Our findings underscore the need to expand health care coverage and preventative medical services for PWID. Furthermore, our findings point to the need to develop comprehensive and coordinated care programs for infected individuals.