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Introduction: It is unknown how long-term prognosis after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis is impacted by cancer-related factors as diagnosis, stage, and treatment. We aimed to assess long-term survival trends after STEMI in this population to evaluate both cardiovascular and cancer-related drivers of prognosis over a follow-up period of 5 years., Methods: In this retrospective single-center cohort study, patients with a prior cancer diagnosis admitted with STEMI between 2004 and 2014 and treated with primary percutaneous coronary intervention (PCI) were recruited from the STEMI clinical registry of our institution., Results: In the 211 included patients, the cumulative incidence of all-cause death after 5 years of follow-up was 38.1% (N = 60). The cause of death was predominantly malignancy-related (N = 29, 48.3% of deaths) and nine patients (15.0%) died of a cardiovascular cause. After correcting for age and sex, a recent cancer diagnosis (< 1 year relative to > 10 years, HR adj 2.98 [95% CI: 1.39-6.41], p = 0.005) and distant metastasis at presentation (HR adj 4.02 [1.70-9.53], p = 0.002) were significant predictors of long-term mortality. While maximum levels of cardiac troponin-T and creatinine kinase showed significant association with mortality (resp. HR adj 1.34 [1.08-1.66], p = 0.008; HR adj 1.36 [1.05-1.76], p = 0.019), other known determinants of prognosis after STEMI, e.g., hypertension and renal insufficiency, were not significantly associated with survival., Conclusions: Patients with a prior cancer diagnosis admitted with STEMI have a poor survival rate. However, when the STEMI is optimally treated with primary PCI and medication, cardiac mortality is low, and prognosis is mainly determined by factors related to cancer stage., (© 2021. The Author(s).)