The objectives of this study were to estimate the prevalence and characterize the epidemiologic patterns of HTLV-1/2 infections and co-infections with HIV, HBV (hepatitis B), HCV (hepatitis C), and Treponema Pallidum in five different high-risk groups, including injecting drug users (IDUs), female sex workers (FSWs), men who have sex with men (MSM), patients with tuberculosis (TB), and patients attending clinics for sexually transmitted infections (STIs) in Buenos Aires, Argentina. The HTLV-1/2 prevalence was 19.1% (33/173) for IDUs, 2.0% (10/613) for FSWs, 2.1% (4/187) for TB, 1.0% (4/400) for STIs and 0.4% (3/282) for MSM, respectively. Among all groups, the higher percentages of co-infection were HTLV-1/HBV (63%, 17/27) and HTLV-1/HCV (52%, 14/27). Among IDUs, there was a high percentage of co-infection of HTLV-2 with HCV (96.3%, 26/27), HIV (92.6%, 25/27), and HBV (77.8%, 21/27), respectively. In summary, HTLV-1/2 infections appear to be widely distributed among high-risk groups in a nonendemic area of Argentina being the co-infection with HBV and HCV more frequent among IDUs.