Objectives: Substantial regional variation in smoking behaviour in Germany has been well documented. However, little is known about how these regional differences in smoking affect regional mortality disparities. We aim to assess the contribution of smoking to regional mortality differentials in Germany over the last four decades.

Design: A cross-sectional study using official cause-specific mortality data by German Federal State aggregated into five macro-regions: East, North, South, West-I and West-II.

Participants: The entire population of Germany stratified by sex, age and region during 1980–2019.

Main outcome measures: Smoking-attributable fraction estimated using the Preston-Glei-Wilmoth method; life expectancy at birth before and after the elimination of smoking-attributable deaths.

Results: In all macro-regions, the burden of past smoking has been declining among men but growing rapidly among women. The hypothetical removal of smoking-attributable deaths would eliminate roughly half of the contemporary advantage in life expectancy of the vanguard region South over the other macro-regions, apart from the East. In the latter, smoking only explains around a quarter (0.5 years) of the 2-year difference in male life expectancy compared with the South observed in 2019. Among women, eliminating smoking-attributable deaths would put the East in a more disadvantageous position compared with the South as well as the other macro-regions.

Conclusion: While regional differences in smoking histories explain large parts of the regional disparities in male mortality, they are playing an increasingly important role for female mortality trends and differentials. Health policies aiming at reducing regional inequalities should account for regional differences in past smoking behaviour.