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Background: Two point CUS (2-CUS) for the diagnosis of symptomatic proximal DVT overlooks calf vein thrombosis (CVT) indicating the need to repeat 2-CUS after one week, which is not cost-effective. Complete CUS (CCUS) of all deep veins from the groin to the ankle in a single procedure will pick up CVT, proximal DVT and isolated ileo femoral DVT plus alternative diagnoses, which is cost-effective. Methodology: We evaluated the combined use of non-invasise 2-CUS versus complete compression ultrasonography (CCUS) and quantitative Elisa D-dimer levels (500, 1000 and 1500 ng/mL) in prospective large management studies between 1998 and 2018 in view of the literature on DVT diagnosis and prevention of DVT recurrence and the post-thrombotic syndrome. Results: Complete compression ultrasonography (CCUS) followed by a sensitive D-dimer test and clinical score assessment is a safe and cost-effective non-invasive strategy to exclude and diagnose deep vein thrombosis (DVT) and alternative diagnoses (AD) in patients with suspected DVT. Rapid and complete recanalization on serial CUS within 3 months post-DVT with no residual venous pathology (RVP-) is associated with low risk of DVT recurrence (1.2% patient/years) and PTS on the basis of which both anticoagulation MECS can be withdraw at 4 months postDVT. Delayed and incomplete recanalization with RVP+ on CUS at 3 months post-DVT is associated with the presence of reflux due to valve destruction, a high risk of DVT recurrence. Symptomatic PTS at 6 to 12 months postDVT have a clear indication to wear MECS for symptomatic relief of PTS symptoms and to extend anticoagulation for one to several years to prevent DVT recurrence. Wearing MECS does not prevent DVT recurrence, reflux and outlet obstruction in symptomatic PTS patients in the original Prandoni and the two large COX and IDEAL prospective randomized clinical studies. The Lower Extremity Thrombosis (LET) extension classification identifies patients with CVT LET class I, proximal DVT LET class II and iliofemoral DVT LET class III at time of acute DVT diagnosis. The higher the LET class the higher the risk of DVT recurrence and PTS. Conclusion: The Villalta score for PTS is not sensitive and specific enough to stratefy for DVT recurrence risk for the indication of extended anticoagulation in post-DVT patients after discontinuation of anticoagulation. Wearing MECS relieves subjective signs of PTS, does not reduce DVT and PE recurrence rate and has no influence on the natural history of PTS. The two randomized clinical trials CaVent and ATTRACT comparing catheter directed thrombolysis followed by anticoagulation versus anticoagulation alone were neither inferior nor superior to anticoagulation for the treatment of acute proximal popliteal-femoral and iliofemoral DVT.