Background Higher levels of socioeconomic deprivation have been consistently associated with increased risk of premature mortality, but a detailed analysis by causes of death is lacking in Belgium. We aim to investigate the association between area deprivation and all-cause and cause-specific premature mortality in Belgium over the period 1998-2019.Methods We used the 2001 and 2011 Belgian Indices of Multiple Deprivation to assign statistical sectors, the smallest geographical units in the country, into deprivation deciles. All-cause and cause-specific premature mortality rates, population attributable fraction, and potential years of life lost due to inequality were estimated by period, sex, and deprivation deciles.Results Men and women living in the most deprived areas were 1.96 and 1.78 times more likely to die prematurely compared to those living in the least deprived areas over the period under study (1998-2019). About 28% of all premature deaths could be attributed to socioeconomic inequality and about 30% of potential years of life lost would be averted if the whole population of Belgium faced the premature mortality rates of the least deprived areas.ConclusionPremature mortality rates have declined over time, but inequality has increased due to a faster pace of decrease in the least deprived areas compared to the most deprived areas. As the causes of death related to poor lifestyle choices contribute the most to the inequality gap, more effective, country-level interventions should be put in place to target segments of the population living in the most deprived areas as they are facing disproportionately high risks of dying.