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Introduction: Tobacco use has significant health consequences in Latin America, and while studies have examined the overall impact, the gender-specific effects have not been thoroughly researched. Understanding these differences is crucial for effective tobacco control policies. The objective of this study was to explore the differences in tobacco-attributable disease and economic burden between men and women in Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, and Peru., Methods: We used a previously validated economic model to quantify the impact of tobacco-related illnesses, including morbidity, mortality, healthcare costs, productivity losses, informal care expenses, and DALYs, by gender and age. We utilized data from national surveys, records, studies, and expert opinions to populate the model., Results: In 2020, there were 351,000 smoking-attributable deaths. Men accounted for 69% and women 31%. Ecuador and Mexico had the highest male-to-female death ratio, while Peru and Chile had the smallest disparities. 2.3 million tobacco-related disease events occurred, with 65% in men and 35% in women. Ecuador and Mexico had higher disease rates among men, while Peru had a more balanced ratio. Regarding DALYs, men lost 6.3 million due to tobacco, while women lost 3.3 million, primarily from COPD, cardiovascular disease, and cancer. Brazil and Mexico had the highest DALY losses for both genders. Costa Rica had a lower male-to-female tobacco use prevalence ratio but ranked second in deaths, disease events, and DALYs attributed to tobacco. Colombia had a unique pattern with a male-to-female death ratio of 2.08 but a higher ratio for disease events. The health systems spent $22.8 billion to treat tobacco-attributable diseases, with a male-to-female cost ratio 2.15. Ecuador showed the greatest gender cost difference, while Peru had the lowest. Productivity loss due to tobacco was $16.2 billion, with Ecuador and Mexico exhibiting the highest gender disparities and Peru the lowest. Informal care costs amounted to $10.8 billion, with men incurring higher costs in Ecuador, Costa Rica, and Mexico., Discussion: Tobacco causes significant health and economic burdens in Latin America, with gender-based differences. There is a need for gender-disaggregated data to improve tobacco control policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alcaraz, Lazo, Casarini, Rodriguez-Cairoli, Augustovski, Bardach, Perelli, Palacios, Pichon-Riviere and Espinola.)