Abstract Background Inequalities in avoidable mortality have been well evaluated in many European countries. We aimed to assess the association between socioeconomic status and avoidable mortality in Italy. Methods The nationwide closed cohort of the 2011 Census of Population and Housing was followed up for 2012- 2019 mortality. Outcomes of preventable and of treatable mortality were evaluated among people aged 30-74. Exposures were education level and residence macro area (North-West, North-East, Center, South-Islands). Adjusted mortality rate ratios (MRRs) were estimated through multivariate quasi-Poisson regression models, by sex and group of causes, taking into account age at death and macro area of residence. Relative index of inequalities (RII) was estimated for preventable, treatable, and non-avoidable mortality and for some specific causes. Results The cohort consisted of 35,708,459 residents (48.8% men, 17.5% aged 65-74), 34% with a high school diploma, 33.5% living in the South-Islands; 1,127,760 deaths were observed, of which 65.2% for avoidable causes (40.4% preventable and 24.9% treatable). Inverse trends between education level and mortality were observed for all causes; comparing the least with the most educated groups, a strong association was observed for preventable (males MRR = 2.39; females MRR = 1.65) and for treatable causes of death (males MRR = 1.93; females MRR = 1.45). Highest RII were observed for HIV/AIDS and alcohol-related diseases (both sexes), drug-related diseases and tuberculosis (males), and diabetes mellitus, cardiovascular diseases, and renal failure (females). Higher risks of preventable and of treatable mortality were found for those living in the South-Islands. Conclusions We documented relevant socioeconomic inequalities in avoidable mortality in Italy, especially in the Southern regions. They represent a possible missed gain in health and suggest a reassessment of priorities and definition of health targets with the lens of equity. Key messages • An inverse socioeconomic gradient in avoidable mortality was observed in Italy, both for preventable and for treatable mortality, with geographical heterogeneity. • Greatest social disparities were found in mortality for causes strongly associated with risk behavior and for which it is possible to identify risk factors on which to intervene.