BACKGROUND: Leukocytosis has been associated with thrombosis and mortality in cancer patients. We explored the association of leukocytosis with venous thromboembolism (VTE) and early mortality in cancer patients initiating chemotherapy. METHODS: Data from a prospective, multicenter observational study of treatment-related complications in 4,405 ambulatory cancer patients initiating chemotherapy was used for this analysis. The association of leukocytosis, VTE and mortality during the course of chemotherapy was evaluated in univariate and multivariate analysis. RESULTS: Ninety-three patients (2.1%) developed VTE and 134 (3%) died over a median follow up of 75 days (range 0-384). Of 4391 patients with available baseline white blood cell (WBC) count, 561 (12.8%) had elevated pretreatment leukocyte counts, defined as WBC > 11 x 10(9) cells/L. VTE occurred in 25 of 561 patients (4.5%) with baseline leukocytosis compared to 68 of 3830 (1.8%) with WBC