Phlegmasia cerulea dolens (PCD) is limb-threatening. Traditional treatments are very morbid. We examine the efficacy of percutaneous treatment of PCD. Between May 2005 and September 2008, we treated 21 limbs in 20 patients with lower extremity PCD who were candidates for thrombolysis. Diagnosis was by clinical examination and duplex ultrasound. Catheter access to the deep venous system was obtained through a popliteal vein. Therapy used pulse spray thrombolysis with tissue plasminogen activator (tPA). Infusion catheters and adjunctive percutaneous techniques were used as indicated. Postoperatively, patients were treated with systemic anticoagulation, compression hose, and interval follow-up. Limbs were graded according to the CEAP classification. Twenty patients (13 male) were treated with a mean age of 55.8 years. Nine patients had hypercoagulable states, four May Thurner syndrome, three a history of cancer, one postcolon resection, one acute myocardial infarction, and one postfemoral vein puncture. All patients had resolution of PCD without the need for open surgery. The initial tPA dose was 19.5 mg with pulse spray thrombolysis. Infusion catheters were required in 18 patients and used for 16.1 hours (range, 8 to 36 hours) until complete thrombolysis. Venous angioplasty was necessary in 14 patients with nine of these requiring venous stents. One patient required above-knee amputation despite successful treatment of her PCD. Mean follow-up was 10.7 months (range, 1 to 39 months). All patients demonstrated no or minimal residual thrombus and intact valvular function and a mean clinical CEAP score of 2.4. Percutaneous treatment of PCD produced excellent results with minimal morbidity.