ObjectivesSummarize hepatitis C virus (HCV) prevalence in injecting (IDU) and non-injecting drug users (NIDU), men who have sex with men (MSM), sex workers, and prison inmates in Latin America and the Caribbean (LAC).MethodsSystematic review on HCV prevalence in sub-populations in LAC. Databases searched from 1-1-2000 to 10-30-2013. Inclusion criteria: prevalence studies in sub-populations in LAC. HCV-antibody was marker for prevalence of current/past HCV infection and HCV-RNA for prevalence of HCV current infection.ResultsIDU HCV current/past infection presented highest prevalence, from 1.7 % in Colombia to over 95 % in Ciudad Juarez and Tijuana, Mexico and pooled regional anti-HCV prevalence was 49 % (CI 95 % 22.6–76.3 %). NIDU, MSM and sex workers anti-HCV prevalence was below 10 %, and pooled regional prevalence of 4 % (CI 95 % 2.6–4.5 %), 3 % (CI 95 % 1.7–4.5 %) and 2 % (CI 95 % 1.0–3.4 %), respectively. Prison inmates presented higher values, but prevalence decreased over the 15-year time span (p < 0.001). Current HCV infection from three countries showed prevalence under 10 % in prison inmates and 1–46 % among drug users.ConclusionsDisease burden is high and surveillance, prevention and treatment should target these groups in LAC.Electronic supplementary materialThe online version of this article (doi:10.1007/s00038-015-0708-5) contains supplementary material, which is available to authorized users.