BACKGROUND. Histological evaluation has a crucial role in diagnosing hepatic diseases and percutaneous liver biopsy (PLB) is widely chosen for this purpose. We aim to describe its indications, the rate and severity of adverse events (AEs) in an outpatient and ultrasound (US)-guided setting over 5 years. METHODS. This observational, single-center, and retrospective study included patients submitted to PLB between 2015 and 2019. We collected age, gender, coagulation tests, comorbidities, and number of needle passes. The association between the variables and outcomes (pain, mild and serious AEs, hospital admission, surgical treatment, and death) was evaluated using the generalized estimating equations method. RESULTS. We analyzed 532 biopsies in 524 patients (55.3% male) aged 49y (13–74y). Almost 39% had cardiovascular comorbidities and 18% had overweight/obesity. Hepatitis C virus (HCV) chronic infection was the major indication for PLB (47%), followed by autoimmune hepatitis/cholestasis (12.6%), and metabolic dysfunction-associated fatty liver disease (MAFLD) (12.1%). The number of HCV-related biopsies had a remarkable reduction, while MAFLD-related procedures have progressively raised over time. Around 54% of the patients reported pain, which was significantly associated with the female gender (p=0.0143). Serious AEs occurred in 11 patients (2.1%); hospital admission was necessary in 10 cases (1.9%), but no patient required surgical approach and there were no deaths. No significant association was found between the occurrence of AEs and the studied variables (clinical, laboratory, and number of needle passes). CONCLUSION. Real-time US-guided PLB is safe to perform in an outpatient setting and its indications have notably undergone a transition from HCV to MAFLD over the years. New strategies to prevent biopsy-related pain are still needed, especially for females.