In this report, we describe a novel technique for the treatment of iliofemoral deep venous thrombosis (DVT) known as the hybrid operative thrombectomy (HOT), which employs a direct infrainguinal approach (by a single incision) with concomitant retrograde advancement of a balloon catheter through femoral venotomy. The purpose of our study was to assess the feasibility, safety, and perioperative and intermediate outcomes associated with this technique. From July 2011 to May 2014, 32 consecutive patients with symptomatic acute or subacute iliofemoral or femoropopliteal DVT were treated with HOT. Exclusion criteria included symptomatic bilateral iliofemoral DVT and caval involvement at the time of diagnosis (n = 4). The primary end points were as follows: (1) angiographic evidence of restored venous patency at completion of the procedure, (2) duplex findings at intermediate follow-up (≥3 months to 3 years), and (3) clinical follow-up by Villalta and CEAP scales. The symptomatic DVT was located at the left limb in 22 of 28 (78.6%) of the cases, the right limb in six of 28 (21.4%). The inferior vena cava and iliofemoral, femoropopliteal, tibial, and great saphenous veins were involved in 0%, 27 of 28 (96.4%), 19 of 28 (67.9%), seven of 28 (17.9%), and three of 28 (10.7%) of the patients, respectively. Balloon angioplasty was completed in 19 of 28 patients (67.9%) and stent placement in 15 of 28 (53.6%). Mean operative time was 100 minutes (range, 40-190 minutes). Complete (>95%) thrombus removal was obtained in 21 of 28 limbs (75%) and partial (between 80% and 90%) resolution in seven of 28 (25%). At a mean follow-up time of 378 days (range, 94-799 days), duplex ultrasound showed chronic nonocclusive DVT at the surgical iliofemoral, femoropopliteal, tibial, and great saphenous vein segments in 16 of 20 (80%), seven of 20 (35%), four of 20 (20%), and four of 20 (20%) limbs (eight of 28 patients lost to follow-up), respectively. Venous reflux at the surgical iliofemoral segment was found to be nonsignificant (reflux time, 0-0.9 second), mild (1-2 seconds), moderate (2-3 seconds), and severe (>3 seconds) in 15 of 20 (75%), four of 20 (20%), 0%, and one of 20 (5%), respectively. Venous reflux at the surgical femoropopliteal segment was found to be nonsignificant, mild, moderate, and severe in 10 of 20 (50%), five of 20 (25%), two of 20 (10%), and three of 20 (15%), respectively. Acute iliofemoral DVT developed in one patient in the early postoperative period and required take back for revision. At a mean follow-up time of 504 days (range, 100-921 days), the clinical CEAP and Villalta scores were 0.85 (range, 0-3) and 2.25 (range, 0-4), respectively. No patients had venous ulcers at follow-up. When it is used as a standalone procedure, the HOT technique can successfully remove venous thrombus safely and effectively and is associated with excellent clinical results at intermediate follow-up.