Deep vein thrombosis (DVT) in critically ill patients still represents a clinical challenge. The aim of the study was to investigate whether a systematic ultrasound (US) screening might improve the management of the antithrombotic therapy in intensive care unit (ICU). In this non-randomized diagnostic clinical trial, 100 patients consecutively admitted to ICU of the University Hospital of Perugia were allocated either in the screening group or in the control group. Subjects in the screening group underwent US examination of lower limbs 48 h after admission, and again after 5 days. Subjects in the control group underwent US examination according to the standard of care (SOC) of the enrolling institution. Retrospectively registered at ClinicalTrials.gov (NCT05019092) on 24.08.2021. Lower limb DVT was significantly more frequent in the screening group (p < 0.001), as well as the subsequent extension of a pre-existing DVT (p = 0.027). In the control group, DVT of large veins was more frequent (p = 0.038). Major bleedings were reported in 5 patients, 4 in the non-screening group and in 1 in the screening group. Patients in the screening group started the antithrombotic treatment later (p = 0.038), although the frequency, dose and duration of the treatment were not different between the two groups. The duration of stay in ICU was longer in the screening group (p = 0.007). Active screening for DVT is associated with an increased diagnosis of DVT. The screening could be associated with a reduced incidence of proximal DVT and a reduction in the bleeding risk.

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