Background/Objectives:
Although smoking-associated mortality (SAM) is a crucial health indicator, research is limited in Portugal. We sought to estimate SAM by region in 2019 in the Portuguese population ≥35 years, highlighting gender differences.

Material and Methods:
A SAM independent-prevalence method was used. Observed mortality was obtained from Portugal Statistics; lung cancer mortality rates in smokers/never-smokers from the Cancer Prevention Study I-II; relative risks from five US cohorts. SAM was estimated for each region by sex, age, and cause of death.

Results:
In 2019, tobacco use caused 12.3% of all deaths in Portuguese adults ≥35 years (men: 17.6%; women: 7.1%). Data broken down by NUTS-II regions show that SAM varies widely by region and gender. Azores depicts the highest SAM, both in males (52.7%) and females (26.8%); the lowest was observed in the Centre among males (24.1%) and in Alentejo among females (9.6%). Regardless of the cause of death and age-group, the highest men-to-women ratios (3-1) were observed in Madeira and Alentejo. SAM specific rates increase with age among males in all regions, whereas among females this pattern is also observed, except in Madeira. According to sex, cancers were the leading cause of death among men in all regions, especially in the North (51.0%); while cardiovascular diseases ranked first among women in all regions, particularly in the Azores (50.7%). Lung cancer was the main specific-cause of death in men, and also among women in Lisbon and Algarve regions. Respiratory diseases caused more deaths among females in the other regions.

Conclusions:
SAM is high and greatly varies by region, gender and age. SAM by gender shows a specific pattern in all regions, although with regional differences among women, suggesting different tobacco epidemic stages by region. There is a need for engendering tobacco control policy-making while monitoring and implementing policies, at national and local level.