BACKGROUND: Human immunodeficiency virus (HIV) outbreaks occur among injecting drug users (IDUs), but where HIV is low insight is required into the future risk of increased transmission. The relationship between hepatitis C virus (HCV) and HIV prevalence among IDUs is explored to determine whether HCV prevalence could indicate HIV risk. METHODS: Systematic review of IDU HIV/HCV prevalence data and regression analysis using weighted prevalence estimates and time-series data. RESULTS: HIV/HCV prevalence estimates were obtained for 343 regions. In regions other than South America/sub-Saharan Africa (SAm/SSA), mean IDU HIV prevalence is likely to be negligible if HCV prevalence is <30% (95% confidence interval 22-38%) but increases progressively with HCV prevalence thereafter [linearly (beta = 0.39 and R(2) = 0.67) or in proportion to cubed HCV prevalence (beta = 0.40 and R(2) = 0.67)]. In SAm/SSA, limited data suggest that mean HIV prevalence is proportional to HCV prevalence (beta = 0.84, R(2) = 0.99), but will be much greater than in non-SAm/SSA settings with no threshold HCV prevalence that corresponds to low HIV risk. At low HCV prevalences (<50%), time-series data suggest that any change in HIV prevalence over time is likely to be much smaller (<25%) than the change in HCV prevalence over the same time-period, but that this difference diminishes at higher HCV prevalences. CONCLUSIONS: HCV prevalence could be an indicator of HIV risk among IDUs. In most settings, reducing HCV prevalence below a threshold (30%) would reduce substantially any HIV risk, and could provide a target for HIV prevention.