Background: VTE is a preventable cause of death within hospitals. This study aimed to assess the association between omission of early thromboprophylaxis for > 24 h after ICU admission and mortality in critically ill patients. Methods: This study involved 175,665 critically ill adult patients admitted to 134 ICUs in Australia and New Zealand between 2006 and 2010. Results: The crude ICU and hospital mortality in patients who did not receive thromboprophylaxis within 24 h of ICU admission was higher than those who were treated with early thromboprophylaxis (7.6% vs 6.3%, P =.001; 11.2% vs 10.6%, P =.003, respectively), despite the former patients being associated with a slightly lower acuity of illness (mean APACHE [Acute Physiology and Chronic Health Evaluation] III model predicted mortality, 13% vs 14%; P =.001). The association between omission of early thromboprophylaxis and hospital mortality remained significant after adjusting for other covariates (OR, 1.22; 95% CI, 1.15-1.30; P =.001), particularly for patients with multiple trauma, sepsis, cardiac arrest, and preexisting metastatic cancer. The estimated attributable mortality effect of omitting early thromboprophylaxis for patients with multiple trauma, sepsis, cardiac arrest, and preexisting metastatic cancer was 3.9% (95% CI, 2.2-5.6), 8.0% (95% CI, 5.6-10.4), 15.4% (95% CI, 11.1-19.8), and 9.4% (95% CI, 6.4-12.4), respectively. Conclusions: Omission of thromboprophylaxis within the first 24 h of ICU admission without obvious reasons was associated with an increased risk of mortality in critically ill adult patients.