From 1979 to 2004, 22 patients were seen with leiomyosarcomas of the inferior vena cava (IVC). Twenty were treated surgically. Involvement of the IVC included the infrarenal segment in 3 cases, the suprarenal and/or retrohepatic segment in 13, and the suprahepatic segment in 4. Nineteen patients underwent wide tumor resection followed by ligation of the IVC in 5 cases, replacement with a PTFE prosthesis in 13, and cavoplasty in 1. An intracardiac tumor extension was resected during hypothermic circulatory arrest in 1 patient. Vascular exclusion of the liver was used in 5 cases and simple clamping of the IVC in 13 cases. There were 1 intraoperative death due to cardiac failure and 3 postoperative deaths due to multiple organ failure, liver failure, and duodenal fistula after treatment of a bleeding ulcer. Fifteen of the 16 surviving patients underwent adjuvant chemotherapy associated with radiation therapy in 4 cases. One patient was lost from follow-up at 10 months. Four patients including one with metastasis are still alive with a mean follow-up of 18.3 months. Eleven patients died after a mean follow-up period of 43.7 months due to local recurrence and/or distant metastasis in 9 cases and complications of chemotherapy in 2. The 3- and 5-year mean actuarial survival rates in patients who underwent resection were 52.0% and 34.8%, respectively. Leiomyosarcoma of the IVC is a serious disease. Although surgical resection combined with chemotherapy is usually not curative, it can achieve reasonably long-term survival. We recommend aggressive operative management using the latest vascular surgery and oncology techniques.