In this study, the prevalence, genotype frequency, and risk factors for HCV infection in 384 cocaine users were determined. One hundred twenty-four (32.3 %) cocaine users had anti-HCV antibodies and 120 (31.3 %) had HCV-RNA. Genotyping results indicated the predominance of genotypes 1 (73.3 %) and 3 (26.7 %). Multivariate analysis showed an association of HCV infection with tattoos, shared use of paraphernalia, daily cocaine use, and a long history of cocaine use. The epidemiological aspects of HCV infection among cocaine users presented here should serve as an incentive for the establishment of a program of hepatitis C prevention and control by the local public-health authorities in the Amazon.