OBJECTIVE Venous lysis is usually reserved for symptomatic patients with acute deep vein thrombosis (DVT) and low risk for bleeding. This study reports the use of pharmacomechanical thrombectomy (PMT) in patients with contraindications to thrombolysis. METHODS A retrospective review of all patients with symptomatic DVT treated between 2007 and 2008 with PMT was performed. All patients were treated by a combination of local tissue plasminogen activator (tPA) with the Angiojet (Possis Medical, Minneapolis, Minn) or Trellis device (Bacchus Vascular, Santa Clara, Calif). Catheter-directed lysis was used sparingly. RESULTS Forty-three patients (mean age, 48.4 +/- 16.6 years) presented with symptoms averaging 13.6 +/- 9.6 days in duration. Nineteen (44%) had symptoms for >14 days, and 15 (35%) had a high risk for bleeding. Symptomatic subclavian thrombosis occurred in eight (19%), and 35 (81%) presented with disabling lower extremity DVT (4 phlegmasia) despite anticoagulation. Fifteen patients had a thrombosed indwelling permanent filter. Sixty-three percent were treated in one session, but 16 patients required a lytic infusion after suboptimal PMT. Iliac stenting was required in 35% of limbs treated. Successful lysis (>50%) was achieved in 95% of patients and symptom resolution in 93%. All patients became ambulatory with no or minimal limitation. There were no major systemic bleeding complications, but access site hematoma occurred in two patients and worsening of pre-existing rectus sheath hematoma requiring transfusion occurred in another two. Limb salvage was maintained in 100% of patients who presented with phlegmasia. Mean follow-up was 5.0 +/- 4.8 months. Freedom from DVT recurrence and reintervention was 95% at 9 months by life-table analysis. CONCLUSIONS PMT can be safely and effectively used for subacute iliocaval and iliofemoral DVT and in patients with contraindications for lytic therapy, resulting in improved functional outcomes relative to their debilitated state before the procedure.