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Objectives Myocardial infarction (MI) is a major contributor to global disease burden with societal impact among survivors. This study aimed to estimate the population-level prevalence of MI among working-age adults in Spain and to examine associated sociodemographic, lifestyle, clinical and occupational factors focusing on sex differences.Design Two-phase population-based study using data from the 2020 Spanish European Health Interview Survey, including adults of working age. First, weighted estimates were used to calculate the population-level prevalence and describe sociodemographic characteristics. Second, a matched cross-sectional analysis was performed to examine associations between MI and sociodemographic, lifestyle, clinical and occupation-related factors using logistic regression models, including sex-stratified analyses.Setting Population-based study in Spain.Participants A total of 400 participants from the Spanish European Health Interview Survey were included, of whom 80 reported MI.Primary and secondary outcome measures Primary outcomes were the prevalence of self-reported MI and its association with sociodemographic characteristics, lifestyle behaviours, comorbidities and working conditions; secondary outcomes included healthcare utilisation and employment-related absences.Results 80 participants reported having a history of MI, corresponding to an estimated 137 646 working-age adults in Spain and a prevalence of 5.45 per 1000 population (95% CI 5.44 to 5.48), predominantly affecting men (74.2%) with a mean age of 52.7 years. MI prevalence was higher among individuals with lower educational attainment (OR 0.50; 95% CI 0.25 to 1); however, no employment-related factors remained associated with MI after adjustment. Sex-stratified analyses revealed that depression (OR 6.75; CI 2.23 to 20.4), obesity (OR 6.36; 95% CI 1.62 to 24.9) and COPD (OR 27.7; 95% CI 4.21 to 749) were more strongly associated with MI among women, while anxiety (OR 8.65; 95% CI 3.09 to 26.8) and hypertension (OR 4.11; 95% CI 2.24 to 7.62) among men.Conclusions MI among working-age adults in Spain is uncommon but concentrated among men with lower levels of education. The absence of independent associations with employment conditions and the presence of sex-specific comorbidity patterns highlight the need for gender-sensitive cardiovascular prevention strategies.