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Background: Transfusion-transmitted infections (TTIs) constitute a major health problem worldwide where routine screening of blood or blood products is improperly done, and where non-medical injecting medications and/or drug use are prevalent. Prevalence and risk factors vary by geographic location and by the specific TTI (including HIV-1, HBV, HCV and HTLV-I)., Objective: To determine the prevalence and risk factors associated with TTIs among a sample of multi-transfused adult patients in Peru., Study Design: A cross-sectional multi-center study was conducted across seven major hospitals in Peru from February 2003 to September 2004. Self-reported behavior information (medical procedures, number of sexual partners, and drug use history) was analyzed, along with a review of exposure history from hospital medical records. Prevalences were calculated by TTI for different exposures, along with unadjusted and adjusted odds ratios for infection risk., Results: Overall, 192 (54.7%) of 351 multi-transfused patients were found infected with one or more TTIs. Number of transfusion units, years of transfusion history (6 or more), and number of treatment facilities (2 or more) were associated with HCV infection. Hemodialysis history was a common risk factor associated with HBV, HCV and HTLV-I infection. HIV infection was associated only with total number of transfusion units received., Conclusions: High prevalences of HBV and HCV infection were found among Peruvian multi-transfused patients and were associated with a past history and number of blood transfusions, as well as with past hemodialysis procedures. TTIs continue to represent a significant public health problem in Peru. Continued vigilant attention to blood safety procedures, including universal screening and health care provider education, is recommended.