OBJECTIVES::  Safety and efficacy of protease inhibitors for chronic hepatitis C (CHC) treatment were showed previously, however, the Brazilian population has been poorly represented in these investigations. Therefore, this study aimed to describe the effectiveness in terms of rapid virological response (RVR) and sustained virological response (SVR) of boceprevir and telaprevir-based regimens as well as safety of these two drugs in Brazil. METHODS::  A prospective longitudinal cohort study was conducted in five public centers in the State of Paraná, South of Brazil. Data from medical charts from adults with CHC genotype 1 with advanced fibrosis (METAVIR score F3 or F4) treated with boceprevir or telaprevir were collected and summarized. Multivariate analysis was performed to investigate the influence of independent variables (i.e. baseline viral load, RVR) on SVR achievement. RESULTS::  A total of 121 patients (15.7% in boceprevir group and 84.3% in telaprevir group) were included. The mean age was 51.0 years, 63.6% were male and 33.1% were cirrhotic. Of the total cohort, 67 patients (55.4%) completed the 48 weeks of treatment (eight in boceprevir group and 59 in telaprevir group). Of the completers, RVR was achieved by 25.0% and 86.4% in boceprevir and telaprevir groups (p<0.001), respectively, and SVR by 75.0% and 81.4% in boceprevir and telaprevir groups (p=0.670), respectively. None of the evaluated factors had influence on SVR. Overall, 148 different adverse events were reported. Nausea was the most frequent adverse event with boceprevir (73.7%) and pruritus with telaprevir (80.2%). Regarding tolerability, 57.9% of patients had the treatment suspended in boceprevir group and 42.2% in telaprevir group. CONCLUSIONS:: SVR was more likely with telaprevir-based regimen than with boceprevir. Both protease inhibitors promoted several adverse events, highlighting the need of measures to improve treatment compliance, particularly in countries where the first-generation DAAs are the only treatment option for CHC patients.