OBJECTIVE: To determine if D-dimer predicts outcomes in critically ill patients. DESIGN: Observational, cohort study. SETTING: Medical intensive care unit (MICU) of a tertiary care hospital. PATIENTS AND PARTICIPANTS: Seventy-four patients consecutively admitted to the MICU. INTERVENTIONS: D-dimer was measured by latex agglutination within 12 h of admission to the MICU. MEASUREMENTS AND RESULTS: Of the study population, 43.2% had positive D-dimers. The in-hospital mortality rate in D-dimer positive patients was 28.1% as compared to 7.1% in D-dimer negative subjects (p = 0.024). D-dimer positive patients had significantly greater frequencies of venous thromboses (21.9% vs 4.8%, p = 0.035). CONCLUSIONS: The D-dimer assay identifies patients at increased risk for mortality and may be a more sensitive test to determine the presence of underlying microvascular pathology in critically ill patients. A positive D-dimer at admission to the MICU is associated with an increased risk for the later development of a venous thromboembolic event (VTE).