Thrombosis of the venous circulatory system represents a serious global health burden. The most common sites, deep vein thrombosis of the lower extremities and pulmonary embolism, collectively known as venous thromboembolism (VTE), may be life-threatening events and are associated with post-thrombotic complications. The overall rate of VTE for people of European ancestry is 1 to 2 per 1000 persons per year (Heit JA. Nat Rev Cardiol. 12(8):464–474, 2015), with increased incidence by age and clinical situation (e.g., greatly increased in people with cancer or postoperative). In the USA alone, there are approximately 300,000 to 600,000 incident events annually (Ortel TL et al. Blood Adv. 4(19):4693–4738, 2020). The estimated annual cost to the US Healthcare system ranges from $7 to $10 billion (Grosse SD et al. Thromb Res. 137:3-10, 2016). A comprehensive understanding of the diagnosis and management of VTE and associated complications is an important part of a hematologist’s knowledge base. Although nearly all clinicians may need to diagnose and treat VTE, clinical hematologists are often consulted on short-term and long-term management questions. Post-thrombotic syndrome (PTS, formerly post-thrombophlebitis syndrome) is a common complication of VTE. Swelling, pain, redness, and skin breakdown are potential complications for acute VTE. In contrast to development of new, effective anticoagulants, interventions to decrease the incidence of PTS have been met with mixed results (Kahn SR et al. Lancet. 383(9920):880–888, 2014). The following cases will highlight risk factors, possible preventive strategies, and management of PTS.