Our purpose was to assess change in HIV and HCV prevalence and risk-taking behaviors among IDUs over a period of time that included changes in French Public Health policy. Risk behavior and biological testing for serostatus were collected from cross-sectional samples of yearly new requests for opiate dependence treatment in Aquitaine, France between 1994 and 2004 (n = 648). Coincident declines in injection equipment sharing and HIV prevalence among injectors were observed, while sexual behavior remained stable. There was a decline in HCV prevalence that was not significant among injectors. After controlling for potential confounding variables, participants enrolled after 1995 were less likely to share injection material and those enrolled after 1999 were less likely to share spoons. Our findings give evidence for behavioral and seroprevalence changes among IDUs over a period of time that included changes in needle access policy.