BACKGROUND: Venous thromboembolism (VTE) prophylaxis remains underutilized, particularly in cancer patients. We explored clinical predictors of prophylaxis in hospitalized cancer patients before the onset of acute VTE. METHODS: In the SWiss Venous ThromboEmbolism Registry, 257 cancer patients (61 +/- 15 years) with acute VTE and prior hospitalization for acute medical illness or surgery within 30 days (91% were at high risk with Geneva VTE risk score ≥ 3) were enrolled. RESULTS: Overall, 153 (60%) patients received prophylaxis (49% pharmacological and 21% mechanical) before the onset of acute VTE. Outpatient status at the time of VTE diagnosis [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18-0.53], ongoing chemotherapy (OR 0.51, 95% CI 0.31-0.85), and recent chemotherapy (OR 0.53, 95% CI 0.32-0.88) were univariately associated with the absence of VTE prophylaxis. In multivariate analysis, intensive care unit admission within 30 days (OR 7.02, 95% CI 2.38-20.64), prior deep vein thrombosis (OR 3.48, 95% CI 2.14-5.64), surgery within 30 days (OR 2.43, 95% CI 1.19-4.99), bed rest >3 days (OR 2.02, 95% CI 1.08-3.78), and outpatient status (OR 0.38, 95% CI 0.19-0.76) remained the only independent predictors of thromboprophylaxis. CONCLUSIONS: Although most hospitalized cancer patients were at high risk, 40% did not receive any prophylaxis before the onset of acute VTE. There is a need to improve thromboprophylaxis in cancer patients, particularly in the presence of recent or ongoing chemotherapy.