AimsThe aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non‐CV, in a large real‐world heart failure (HF) population across the ejection fraction (EF).Methods and ResultsPatients with HF from the Swedish HF Registry between 2000‐2021 were included. Of 91,463 patients (median age 76 years [IQR 67–82]), 98% had at least one among the 17 explored comorbidities (94% at least one CV and 85% at least one non‐CV comorbidity). All comorbidities, except for coronary artery disease (CAD), were more frequent in HF with preserved EF (HFpEF). Patients with multiple comorbidities were older, more likely female, inpatients, with HFpEF, worse NYHA class and higher NT‐proBNP levels. In a multivariable Cox model, 12 comorbidities were independently associated with a higher risk of death from any cause. The highest risk was associated with dementia (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.45‐1.65), chronic kidney disease (HR 1.37, 95%CI 1.34‐1.41), chronic obstructive pulmonary disease (HR 1.32, 95%CI 1.28‐1.35). Obesity was associated with a lower risk of all‐cause death (HR 0.81, 95%CI 0.79‐0.84). CAD and valvular heart disease were associated with a higher risk of all‐cause and CV mortality, but not non‐CV mortality, whereas cancer and muscolo‐skeletal disease increased the risk of non‐CV mortality. A significant interaction with EF was observed for several comorbidities. Occurrence of CV and non‐CV outcomes was related to the number of CV and non‐CV comorbidities, respectively.ConclusionThe burden of both CV and non‐CV comorbidities was high in HF regardless of EF, but overall higher in HFpEF. Multimorbidity was associated with a high risk of death with a different burden on CV or non‐CV outcomes.This article is protected by copyright. All rights reserved.