Objective To evaluate risk factors related to Hepatitis C treatment interruption. Methods Retrospective cohort of patients seen at the Hepatology outpatient service at Hospital dos Servidores do Estado do Rio de Janeiro, from 2001 to 2009. The factors investigated were: age, gender, genotype, degree of liver fibrosis, type of treatment, treatment time in weeks, diabetes mellitus, and systemic hypertension. Survival curves and bivariate and multivariate Cox regression models were used in the analyses. Results The risk of treatment interruption is six times greater in patients with more advanced degrees of liver fibrosis (F4) compared to those with less advanced degree (F2) in the period from 0 to 24 weeks of treatment. Genotype was found to be an important factor to explain therapy cessation after 24 weeks of treatment – the risk of stopping treatment was 2.5 times higher in patients with genotype 3 than in those with genotype 1. Conclusion Degree of liver fibrosis and genotype proved to be the main risk factors associated to treatment interruption.