Background Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with unknown etiology. The prognosis of patients affected by PBC is heterogeneous, with a relevant improvement achieved after the introduction of ursodeoxycolic acid (UDCA). Since in the last years obeticholic acid (OCA) has been approved for the combined treatment of PBC, in patient non-responders to UDCA or as monotherapy in those intolerant to UDCA, we evaluated the response to UDCA in a cohort of patients with PBC managed in a specialistic setting. Methods We included 38 UCDA-treated non-cirrhotic, early-PBC patients. Data were retrieved from documents compiled during the annual follow-up. The response to therapy was assessed comparing the parameters of our cohort with the inclusion criteria of the POISE Trial and the Paris I and Paris II criteria. Results The cohort included 34/38 female patients and the average age was 65.34±10.69 years. Over 50% of the patients were affected by at least one disease associated to PBC. Using the POISE criteria and the Paris I and Paris II criteria, we identified 5, 2 and 5 non-responders, respectively. All patients with severe fibrosis had a biochemical response to UDCA according to the three different criteria applied. No side effect was reported. Conclusions We confirm that UDCA is a safe and effective treatment in patients with PBC. Non-responder patients represent 13% of our population, with high risk of disease progression and complications. In this context, further therapy using OCA should be considered.