OBJECTIVES: To estimate the prevalence and determine the clinical presentation of risk factors of hepatitis C virus (HCV) among HIV-infected patients in Bissau, Guinea-Bissau. METHODS: In this cross-sectional study, we included individuals who had a routine blood analysis performed during the period April 28 to September 30, 2011. Patient samples were tested for HCV antibodies (anti-HCV) with a chemiluminescence test (Architect, Abbott, USA) and INNO-LIA HCV Score (Innogenetics, Belgium). HCV viral load and genotype were analyzed using an in-house real-time PCR method. RESULTS: In total, 576 patients were included (417 HIV-1, 104 HIV-2, and 55 HIV-½). Ten (1.7%) patients were anti-HCV-positive and eight (1.4%) patients had detectable HCV RNA; all were genotype 2. In a multivariable logistic regression analysis, age >50 years was associated with anti-HCV reactivity (p<0.01). No subjective symptoms or objective signs were more prevalent among patients with detectable HCV RNA compared to patients without detectable HCV RNA. Biochemically, detectable HCV RNA was associated with elevated amylase (83.3% vs. 38.6%, p=0.03), but not with the liver enzymes alanine aminotransferase and aspartate aminotransferase. CONCLUSIONS: The prevalence of anti-HCV was low and comparable to similar settings, and genotype analysis confirmed the presence of genotype 2 in West Africa.