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BackgroundCardiovascular disease has traditionally been studied predominantly in men, but understanding its manifestations in women is crucial for effective management. This study aims to evaluate the long-term prognosis of female patients with acute coronary syndrome (ACS) within a tertiary hospital setting in Spain.MethodsRetrospective observational study based on a cohort of consecutive hospitalized patients with ACS from January 2009 to December 2014. Data on demographics, risk factors, treatment, and outcomes were collected, with a median follow-up of 9.2 years.ResultsWomen with ACS, constituting 27.3% of 2,330 patients, were older and had a higher prevalence of cardiovascular risk factors such as obesity, hypertension, and diabetes mellitus compared to men. They presented with more non-ST-segment elevation myocardial infarction and underwent less coronary angiography. Female patients were also less likely to be treated with acetylsalicylic acid, a second antiplatelet drug, or statins. Despite initial higher mortality rates [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.13–1.49; p < 0.001], female patients exhibited a more favorable long-term prognosis after adjustments (adjusted HR 0.82; 95% CI 0.71–0.96; p = 0.014), even in the subgroup analysis excluding patients with unstable angina.ConclusionsWomen with ACS are more comorbid, but after adjustments, female sex appears to be a protective factor that confers a better long-term prognosis.