Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. Results: 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma HCC prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% 95% CI: 87.6–98.7 vs. 97.7% 95% CI: 85.0–99.7%, p = 0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR = 8.71 95% CI: 3.17–23.99). SVR was associated with regression of APRI (OR = 26.00 95% CI 4.27–1065.94) and FIB-4 (OR = 15.00 95% CI: 2.30–631.47). Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.