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Patients with acute pulmonary embolism (PE) have a wide spectrum of clinical presentations, from incidental findings to sudden cardiac death. Management and treatment recommendations in currently available guidelines vary according to patient risk and haemodynamic profile. A clot-in-transit (CiT) in the right heart chambers may be occasionally identified and is, therefore, an under-recognised but challenging condition, often preceding an abrupt clinical deterioration, and associated with increased mortality. Data on the detection of a CiT are sparse but consistent in attributing negative prognostic relevance, and therefore the presence of CiT should be systematically investigated and recorded in the setting of PE.In this review, the challenges related to the identification of a CiT are highlighted. Here, we propose an algorithm where the role of the Pulmonary Embolism Response Team (PERT) is reinforced. The PERT should convene once the CiT is suspected, to define the timeline for the diagnostic steps and subsequent management on a case-by-case basis. A patient with PE and CiT requires close bedside monitoring and rapid escalation therapy in case of clinical deterioration. Beyond anticoagulation alone, more aggressive strategies can be considered, including systemic thrombolysis, surgical pulmonary embolectomy and the currently emerging catheter-directed therapies. PROSPERO registration number: CRD42024493303., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)