Post-Thrombotic Syndrome (PTS) develops frequently (25-50%) in patients with proximal deep vein thrombosis (DVT) despite the use of standard anticoagulant therapy. PTS leads to lifestyle-limiting symptoms, work disability, leg ulcers, quality of life (QOL) impairment, and major healthcare costs. Preliminary studies indicate that image-guided Endovascular Thrombus Removal procedures can rapidly restore deep venous patency and thereby prevent PTS in acute proximal DVT patients. However, these studies are limited by reliance upon surrogate anatomic outcome measures of limited clinical significance, non-randomized design, single-center design, and small sample size. For this reason, there currently exists major controversy within the medical community as to whether or not Endovascular Thrombus Removal should be routinely used in the first-line treatment of acute proximal DVT. The long-term goal of the proposed project is to determine whether Endovascular Thrombus Removal should be translated into widespread, first-line use in patients with acute DVT. In the proposed study, we will conduct a Phase III, multicenter, open label, assessor-blinded, randomized controlled trial entitled "Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT)" to determine whether the use of Pharmacomechanical Catheter-Directed Thrombolysis (PCDT), a state-of-the-art Endovascular Thrombus Removal method, results in a) a lower prevalence of PTS and b) superior quality of life (QOL), two clinically important treatment outcomes, in symptomatic, first episode, acute proximal DVT patients. The proposed research is both innovative and significant. The study will be the first multicenter randomized trial to evaluate a state-of-the-art image-guided endovascular strategy for the prevention of PTS. If the study establishes a favorable risk-benefit ratio for PCDT, this finding will fundamentally change clinical practice and enable prevention of PTS in thousands of DVT patients. If PCDT does not prevent PTS or if its risk-benefit ratio proves to be unfavorable, this finding will reduce or eliminate the routine use of a costly and potentially risky therapy. Hence, either outcome of the proposed study will greatly improve clinical practice and decrease morbidity in patients with acute DVT, a common blood disorder. Therefore, the study will clearly improve public health and advance the NHLBI's mission. Project Narrative: The ATTRACT Trial will determine whether Pharmacomechanical Catheter-Directed Thrombolysis can prevent the Post-Thrombotic Syndrome (PTS) in patients with Deep Vein Thrombosis (DVT). If the Trial is positive, this finding will conclusively validate the "Open Vein Hypothesis" and thereby a) immediately enable prevention of PTS, a common, morbid, and expensive condition, in thousands of DVT patients each year;and b) catalyze a fundamental shift towards a new treatment paradigm in which early venous thrombus removal is considered an essential element of initial DVT therapy. If the Trial is negative, this finding will eliminate the routine use of a costly and potentially dangerous therapy. Hence, either study outcome will decrease morbidity from DVT, improve public health, and advance the NHLBI's mission.