Abstract Background In case of liver tumor, surgical resection is the therapeutic gold standard to increase patient survival. Among liver resections, right hepatectomy (RH) is defined as a major hepatectomy. The first aim of this study was to analyze the overall morbidity and mortality of patients undergoing RH, the second aim was to assess changes in both patients characteristic and surgical parameters and mortality rates in a single center institution. Materials From 2001 to December 2015, 225 RH were performed in our center. We analyzed two time period: 2001–2007 and 2008–2015. Results Ninety days post operative mortality was observed in 9 cases (4%) for the overall cohort. We observed a difference between the two groups in the use of Pringle Maneuver (p < 0,001). This result is consistent in each major surgical indication: HCC (p = 0,001), CLM (p = 0,015) and BT (p = 0,015). The estimated blood losses improved (p = 0,028), particularly for the HCC cases (p = 0,024). No difference was observed in terms of number of transfusions received between the two groups. Reduced length of stay was observed in the second group (p < 0,001), more markedly for CLM cases (p = 0,001). Conclusion To further improve the outcomes of RH, it is important to performed this major hepatectomy in hepatobiliary centers with an overall liver resection experience of at least few hundred cases.