A constant and progressive increase in the availability of heroin in Colombia in recent decades and the intravenous use of this drug have established the need to prevent a possible epidemic of HIV and hepatitis C. This research determined the sero-prevalence of hepatitis C and HIV according to sociodemographic characteristics and risk behaviors in people who inject drugs in Armenia, Colombia. This is a cross-sectional study on 265 users captured through respondent-driven sampling after informed consent. Sero-prevalence of hepatitis C was 22.3 % [95% CI 12.3 % -23.5 %]; for HIV infection, it was 2.6 % [95% CI 0.4 to 6.0]; 67.5% reported injecting for more than two years, 35 % shared needles and syringes, and 12.4 % had used a condom during their last sexual intercourse. Users who did not purchase syringes in drugstores in the last six months are 2.7 times [95% CI 1.32 to 5.48] more likely to contract hepatitis C; daily injection frequency was higher in HIV- positive cases [OR 2.87; 95% CI 0.55 to 15.9] but nonsignificant. One fourth of respondents are infected with HIV or hepatitis C, either as a single infection or co-infection. This study identified risk practices such as sharing needles and low condom use in the last six months, worldwide documented and discussed risk factors. This research is a first step in the search for strategies to prevent the spread of HIV infection and hepatitis C in networks of injecting drug users.