Background: Multimorbidity (two or more comorbidities) is common among patients with acute heart failure, but comprehensive global information on its prevalence and clinical consequences across different world regions and income levels is scarce. This study aimed to investigate the prevalence of multimorbidity and its effect on pharmacotherapy and prognosis in participants of the REPORT-HF study., Methods: REPORT-HF was a prospective, multicentre, global cohort study that enrolled adults (aged ≥18 years) admitted to hospital with a primary diagnosis of acute heart failure from 358 hospitals in 44 countries on six continents. Patients who currently or recently participated in a clinical treatment trial were excluded. Follow-up data were collected at 1-year post-discharge. The primary outcome was 1-year post-discharge mortality. All patients in the REPORT-HF cohort with full data on comorbidities were eligible for the present study. We stratified patients according to the number of comorbidities, and countries by world region and country income level. We used one-way ANOVA, χ 2 test, or Mann-Whitney U test for comparisons between groups, as applicable, and Cox regression to analyse the association between multimorbidity and 1-year mortality., Findings: Between July 23, 2014, and March 24, 2017, 18 553 patients were included in the REPORT-HF study. Of these, 18 528 patients had full data on comorbidities, of whom 11 360 (61%) were men and 7168 (39%) were women. Prevalence rates of multimorbidity were lowest in southeast Asia (72%) and highest in North America (92%). Fewer patients from lower-middle-income countries had multimorbidity than patients from high-income countries (73% vs 85%, p<0·0001). With increasing comorbidity burden, patients received fewer guideline-directed heart failure medications, yet more drugs potentially causing or worsening heart failure. Having more comorbidities was associated with worse outcomes: 1-year mortality increased from 13% (no comorbidities) to 26% (five or more comorbidities). This finding was independent of common baseline risk factors, including age and sex. The population-attributable fraction of multimorbidity for mortality was higher in high-income countries than in upper-middle-income or lower-middle-income countries (for patients with five or more comorbidities: 61% vs 27% and 31%, respectively)., Interpretation: Multimorbidity is highly prevalent among patients with acute heart failure across world regions, especially in high-income countries, and is associated with higher mortality, less prescription of guideline-directed heart failure pharmacotherapy, and increased use of potentially harmful medications., Funding: Novartis Pharma., Translations: For the Arabic, French, German, Hindi, Mandarin, Russian and Spanish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JGFC reports grants and personal fees from Amgen, Bayer, Bristol Myers Squibb, and Torrent Pharmaceuticals; personal fees from AstraZeneca, Myokardia, Servier, and Abbott; grants, personal fees, and non-financial support from Medtronic, Novartis, and Vifor; and grants and non-financial support from Pharmacosmos and PharmaNord. UD reports research support from AstraZeneca, Pfizer, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Boston Scientific; and speaker's honoraria and consultancies from AstraZeneca, Novartis, and Amgen. GE reports personal fees from AstraZeneca, Abbott, Boehringer Ingelheim, Novartis, and Vifor, all outside the submitted work; non-financial support from the University Hospital Würzburg, and the Comprehensive Heart Failure Center Würzburg; and grant support from German Ministry for Education and Research (BMBF). SVP reports support from Novartis for the present manuscript; consulting fees from Abbott and Bago; and personal fees from Abbott, Boehringer Ingelheim, and Bago. MG and AO were formerly Novartis employees. AS is employed by Novartis. SPC reports research grants from the National Institutes of Health, Agency for Research and Quality, American Heart Association, and the Patient-Centered Outcomes Research Institute; and consulting fees from Novartis, Medtronic, Aiphia, Boehringer Ingelheim, Siemens, and Ortho Clinical. GF reports research grants from the EU; committee fees from Novartis related to REPORT-HF; and lecture fees or being a committee member in trials or registries sponsored by Servier, Boehringer Ingelheim, Medtronic, Vifor, Amgen, and Bayer. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board, Steering Committee, or Executive Committee for Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma, EchoNous, Eli Lilly, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development, Medscape WebMD Global, Merck, Novartis, Novo Nordisk, Prosciento, Radcliffe Group, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as co-founder and non-executive director of Us2.ai. JT has received consulting or speaker fees from Daiichi-Sankyo, Boehringer Ingelheim, Roche Diagnostics, and Us2.ai; and owns patent US-10702247-B2 unrelated to the present work. CEA reports grant support, personal fees, or non-financial support from Abbott, AstraZeneca, Boehringer Ingelheim, Medtronik, Novartis, Novo Nordisk, Radcliffe Group, and Vifor Pharma, all outside of the submitted work; and acknowledges non-financial support from the University Hospital Würzburg, and the Comprehensive Heart Failure Center Würzburg, and grant support from BMBF. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)