Introduction. Randomized clinical trials and meta-analyses demonstrate the efficacy of fibrate therapy in ursodeoxycholic acid (UDCA)-resistant patients with primary biliary cirrhosis (PBC). However, there is still limited information on the efficacy and safety of fenofibrate use in routine clinical practice in PBC. Aim. To evaluate the efficacy and safety of fenofibrate therapy in outpatients with PBC, who have an insufficient response and/or are intolerant to UDCA. Materials and methods. A retrospective assessment of treatment response (complete biochemical response, Paris-II, GLOBE scores), adverse events, and disease progression was performed in 63 patients with PBC refractory to UDCA monotherapy, receiving fenofibrate at 145–200 mg daily in combination with UDCA at 13–15 mg/kg/day for at least 6 months (average 21.0 ± 12.8 months). The mean disease duration before diagnosis was 35.4 ± 38.4 months, and the proportion of patients with advanced-stage PBC before therapy was 68.3%. Results. Paris-II, GLOBE and complete biochemical response rates were 54.0%, 58.7% and 25.4%, respectively, and were negatively associated with the presence of clinically significant portal hypertension (CSPH) (p = 0.0006, p = 0.006, p = 0.001, respectively). The addition of fenofibrate to UDCA reduced the incidence of skin itching from 60.6% to 18.2% (p = 0.0005). The following adverse events (AE) were reported during fenofibrate therapy: myalgia (n = 10); asymptomatic cholecystolithiasis (n = 6); an increase in ALT by 5 or more times from baseline levels, which regressed upon drug discontinuation (n = 2); one patient had a serious AE – bleeding from esophageal varices, probably not related to the medication. A 1.7-fold increase in the incidence of anemia associated with comorbid conditions was noted. Fenofibrate therapy was not associated with a statistically significant increase in the incidence of advanced-stage PBC, clinically significant portal hypertension, or the MELD score in patients with cirrhosis. Conclusions. The addition of fenofibrate to UDCA in UDCA-refractory PBC increases the response rate and appears to be quite safe.