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Rasha A Al-Khafaji,1,2 Louise Schierbeck1 1Cardiology Department, Nordsjælland (North Zealand) University Hospital, Hillerød, Denmark; 2Endocrinology and Nephrology Department, Nordsjælland (North Zealand) University Hospital, Hillerød, DenmarkCorrespondence: Rasha A Al-Khafaji; Louise Schierbeck Tel +45 31 32 11 89; +45 48 29 52 15Email rasha.alkhafaji2@gmail.com; louise.schierbeck@gmail.comAbstract: Modern diagnostic strategies of venous thromboembolism (VTE) have been developed. In this review, the diagnostic algorithms for deep-vein thrombosis (DVT) and their parameters are discussed individually in the context of reporting a case of DVT in a 43-year-old Caucasian female with a moderate pretest probability stratified by Wells’ score and a negative high quality D-dimer test. The patient was on treatment with Xarelto (rivaroxaban), 20 mg PO daily at the time of presentation. The diagnosis was verified through a complete lower limb ultrasound (US). This case highlights the diagnostic challenges and pitfalls of the current algorithms, especially those seen in a subgroup of patients such as patients with cancer, pregnancy, recurrent VTE or are on anticoagulation therapy at the time of presentation. The diagnosis of DVT is less plausible in a patient who is on anticoagulation therapy, but physicians should be aware of such a possibility. Physicians should also know in advance the numerous clinically relevant limitations of D-dimer testing before interpreting the results. Unifying the current diagnostic strategies, modifying the current Wells’ score and using the protocol of a whole-leg compression US instead of the limited US protocol are among the several cautious suggestions that have been proposed based on this review to possibly decrease the incidence of missed DVT.Keywords: compression ultrasound, recurrent thrombosis, rivaroxaban, Wells’ score