IMPORTANCE There is limited data on the prevalence and mortality of venous thromboembolism (VTE) following oncologic surgery. OBJECTIVE To evaluate the trends, factors, and mortality of VTE following major cancer surgery. DESIGN, SETTING, AND PARTICIPANTS Patients undergoing colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy, or prostatectomy were identified retrospectively using the Nationwide Inpatient Sample between January 1, 1999, and December 30, 2009, resulting in a weighted estimate of 2 508 916 patients. MAIN OUTCOMES AND MEASURES Venous thromboembolism following major cancer surgery was assessed according to date, patient, and hospital characteristics. The determinants of in-hospital VTE were evaluated using logistic regression analysis. RESULTS Venous thromboembolism showed an estimated annual percentage increase of 4.0% (95% CI, 2.9% to 5.1%), which contrasts with a 2.4% (95% CI, –4.3% to –0.5%) annual decrease in mortality in VTE after major cancer surgery. In multivariate logistic regression analysis, older age (odds ratio OR, 1.03; P < .001), female sex (OR, 1.25; P < .001), black race (vs white; OR, 1.56; P < .001), Charlson comorbidity index score of 3 or more (OR, 1.85; P < .001), and Medicaid (vs private insurance; OR, 2.04; P < .001), Medicare (OR, 1.39; P < .001), and uninsured (OR, 1.49; P < .001) status were associated with an increased risk of VTE. Conversely, other (nonwhite and nonblack) race (OR, 0.75; P < .001) was associated with a lower risk of VTE. Among hospital characteristics, urban location (OR, 1.32; P < .001) and teaching status (OR, 1.08; P = .01) were associated with greater odds of VTE. Patients with vs without VTE experienced 5.3-fold greater odds of mortality. CONCLUSIONS AND RELEVANCE During our study period, VTE events following major cancer surgery increased in frequency; however, associated VTE mortality decreased. Changing VTE detection guidelines and better management of this condition may explain our findings.