OBJECTIVE Invasion of the inferior vena cava (IVC) by tumor is generally considered a criterion of unresectability. This study was designed to review the outcomes of a strategy of aggressive resection of the vena cava to achieve complete tumor resection coupled with prosthetic graft placement to re-establish caval flow. METHODS Retrospective review of patients treated at a university referral center. Ten patients (mean age 54; eight females, two males) underwent tumor resection that involved circumferential resection of the IVC and immediate prosthetic replacement with ringed polytetrafluoroethylene (PTFE) grafts ranging in diameter from 12 to 16 mm. RESULTS Seven patients had replacement of the infrarenal IVC, two of their suprarenal IVC, and one had reconstruction of the IVC bifurcation. Four of the 10 patients received preoperative chemotherapy, and none received radiotherapy. The most common (7/10) pathologic diagnosis was leiomyosarcoma arising from the IVC or retroperitoneum. Additional diagnoses included teratoma (one), renal cell carcinoma (one), and adrenal lymphoma (one). There were no perioperative deaths, and one complication (prolonged ileus) occurred. Mean length of stay was 8.1 days. Anticoagulation was not routinely used intraoperatively or postoperatively. Follow-up (mean duration = 19 months) demonstrated that survival was 80% (8/10) and 88% (7/8) of patients were free of venous obstructive symptoms. CONCLUSIONS Resection of the IVC with prosthetic reconstruction allows for complete tumor resection and provides durable relief from symptoms of venous obstruction.