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Background The EPIPHANY decision tree is the first algorithm developed to predict serious complications in patients with cancer and pulmonary embolism (PE) (PMID: 28267709). Methods The objective is to evaluate the discriminatory ability of EPIPHANY in a prospective multicenter cohort. Patients with PE diagnosed by objective methods were recruited from October 2017 to April 2019. The association between the increase in prognostic category and in complications at 15 days was assessed using the linear by linear association test. Results The sample contains 463 patients with PE (39.7% suspected and 60.3% unsuspected). 68.3% (n = 316) showed clinical or haemodynamic instability, while 31.7% (n = 147) were normotensive PE with apparent clinical stability. The breakdown of initial risk criteria is: sudden or progressive dyspnea (58.7%), tachycardia >110 lpm (17.3%), hypotension 30 rpm (3.2%), thrombopenia Conclusions EPIPHANY is the only model available for the classification of patients with cancer and PE, based on their short-term risk of complications, with potential implications for decision making. Legal entity responsible for the study Asociacion de Investigacion de la Enfermedad Tromboembolica Venosa de la Region de Murcia. Funding Leo Academy. Disclosure M. Sanchez Canovas: Research grant / Funding (institution): Leo Pharma. All other authors have declared no conflicts of interest.