Introduction - A decline in the incidence rates of acute coronary syndromes (ACS) and associated mortality has been observed in the Western world over the past three decades, including in France. We sought to determine whether there were geographical disparities within France in these decreases between 2006 and 2016. Methods - We analyzed three population-based registries covering the European metropolis of Lille in northern France, the Bas-Rhin department in northeastern France, and the Haute-Garonne department in southwestern France. All ACS cases (fatal and non-fatal hospitalizations and all out-of-hospital deaths due to ACS) among men and women aged 35 to 74 residing in these three geographic areas were recorded between 2006 and 2016. Rates were standardized to the total population. Crude rates were calculated by 10-year age group. Results - Each geographic region recorded a significant decline in ACS incidence rates over the 11-year period, among both men and women, with the largest decline observed in Toulouse (-2.2% per year among men and -2.4% per year among women). However, this decline was only observed after age 54 in men and age 64 in women, across all three regions. Incidence (first events) also decreased over the period in both sexes in Toulouse (-1.3% per year among men and -1.9% per year among women), but only among men in Lille (-1.4% per year) and Strasbourg (-0.7% per year). These decreases were observed only among men and women aged 65 to 74. As for coronary mortality, it decreased significantly in all three regions over the period. The most notable decline is observed in Toulouse (-5.6% per year among men and -8.3% per year among women) because mortality decreased in this region across all age groups and both sexes, unlike the other regions, which show declines only among older individuals. As for 28-day mortality, it remains lower in Toulouse (24%) compared to Lille (34%), with Strasbourg falling in between (29%). Conclusion - Declining trends in ACS rates and incidence were observed between 2006 and 2016 among men and women aged 35 to 74, consistently across three distinct French geographic regions. This effect can be primarily attributed to the decrease in the incidence rate of ACS among individuals aged 65 to 74. In contrast, regional disparities were observed regarding mortality. Indeed, mortality declined across all age groups and in both sexes in Toulouse, whereas it declined only among the oldest age group in Lille and Strasbourg. Despite these favorable trends, the decreasing north-south gradient still persists. Primary and secondary prevention measures must therefore be further strengthened—particularly in the north and east of the country, as well as among young adults—to further reduce these rates in these regions.