The recurrence of HCV infection after liver transplantation was the main cause of mortality and loss of graft in transplanted patients until the use of direct-acting antivirals (DAAs). We performed a monocentric retrospective study from November 2014 to September 2017 at "Ospedali Riuniti", Ancona, Italy, to evaluate the outcome and tolerability of DAAs after liver transplantation. In total, 55 patients with HCV recurrence after liver transplantation treated with DAAs were included. The most frequent genotype was genotype 1a (36%), followed by genotype 3a (27%). The majority of the patients presented a mild or moderate hepatic fibrosis (METAVIR score of F0 -F1 in 20% and F2 in 27%). The patients received sofosbuvir + daclatasvir, sofosbuvir + ribavirin, sofosbuvir + simeprevir, sofosbuvir + ledipasvir, and sofosbuvir + velpatasvir in 54%, 18%, 13%, 13%, and 2% of the cases, respectively, for 12 or 24 weeks. The SVR 12 rate was 89% overall, without a statistically significant relationship with genotypes, fibrosis stage, and therapy. Moreover, 52% of the patients modified the dosage of tacrolimus in the first three months of therapy with DAAs, without statistical significance compared to the group that not changed tacrolimus dosage. The most frequent adverse events were anemia associated with ribavirin. IFN-free treatment with DAAs is highly effective for HCV relapse after liver transplantation and it showed high tolerability in our patients.