IMPORTANCE Vascular leiomyosarcomas are a rare subtype of leiomyosarcomas that most commonly affect the inferior vena cava and account for 5%of all leiomyosarcomas. These tumors are aggressive malignant tumors for which adjuvant modalities have not shown increased efficacy compared with surgery. OBJECTIVES To evaluate the outcomes of patients with vascular leiomyosarcoma and the association between vascular leiomyosarcomas and immunohistochemical molecular markers, to determine their potential prognostic and therapeutic utility. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review of a cohort of 77 patients who presented to the University of Texas MD Anderson Cancer Center in Houston during the period from January 1993 to April 2012. Data were analyzed during the period from November 2012 to May 2015. All of the patients received a confirmed diagnosis of vascular leiomyosarcoma. Immunohistochemical studies for biomarkers were performed on a tissue microarray that included 26 primary specimens of vascular leiomyosarcoma. MAIN OUTCOMES AND MEASURES Demographic and clinical factorswere evaluated to assess clinical course, patterns of recurrence, and survival outcomes for patients with primary vascular leiomyosarcoma. A univariate Cox proportional hazards model was used to correlate disease-specific survival and time to recurrence with potential prognostic indicators. RESULTS Sixty-three patients with localized disease who underwent surgical resection formed the study population, and their data were used for subsequent outcomes analysis. The median age at diagnosis was 58 years (range, 22-78 years). The majority of patients were female (41 patients [65%]) and white (51 patients [81%]). The 5-year disease-specific survival rate after tumor resection was 65%. The median time to local recurrence was 43 months, the median time to distant recurrence was 25 months, and the median time to concurrent local and distant recurrences was 15 months (P = .04). Strong expressions of cytoplasmic β-catenin (hazard ratio, 5.33 [95%CI, 0.97-29.30]; P = .06) and insulinlike growth factor 1 receptor (hazard ratio, 2.74 [95%CI, 1.14-6.56]; P = .02) were associated with inferior disease-specific survival. CONCLUSIONS AND RELEVANCE Vascular leiomyosarcomas are aggressive malignant tumors, with high recurrence rates. Expressions of β-catenin and insulinlike growth factor 1 receptor were associated with poor disease-specific survival. Prospective studies should evaluate the clinical and therapeutic utility of these molecular markers.