Post-thrombotic syndrome (PTS) refers to chronic manifestations of venous insufficiency following a deep-vein thrombosis (DVT). It is a frequent, chronic, burdensome and costly disease for which therapeutic options are limited. Above all, the optimal management of PTS consists of preventing its occurrence: first, by preventing DVT, and second, by preventing development of PTS after a DVT. Prevention of DVT is challenging, particularly in the case of nonsurgical hospital inpatients, where physician’s adherence to recommended thromboprophylaxis is often low. In our opinion, this adherence should be improved by generalizing the use of multi-component approaches, including that of automatic reminders. For prevention of PTS after an acute DVT, our recommendations are as follows. After a proximal (popliteal and above) DVT we recommend early ambulation with daily use of 30–40 mmHg graduated elastic compression stockings (ECS) for two years, in addition to careful monitoring of anticoagulant therapy. Below-knee ECS are preferred to thigh-length ECS, as they have similar efficacy in preventing PTS and are better tolerated. To improve compliance with ECS, patient education is important, and use of lighter strengths of compression in patients not tolerating traditional strengths should be considered. Catheter-directed thrombolysis of acute DVT was recently shown to be effective in preventing PTS, but we believe that confirmatory studies are needed before recommending its general use. The cornerstone of management of established PTS relies on patient education and use of compression therapy. We encourage ambulation, use of ECS to manage symptoms, and participation in an exercise training program, which has the potential to improve patients’ quality of life (QOL) and PTS scores. In the absence of symptom relief, ECS that provide a higher strength (40–50 mmHg) should be tried. In case of moderate to severe PTS, intermittent compressive devices can be used to improve PTS symptoms. Surgery and endovascular procedures, including balloon angioplasty, stent placement, endovenectomy or valve reconstruction should be considered only in specialized centers, and only for patients with severe PTS for whom previous conservative treatment has failed. These techniques are still under evaluation and the level of evidence supporting their use is low.