To evaluate the diagnostic performance of a quantitative, immunoturbidimetric D-dimer assay and compare it with other components of the proposed International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) diagnostic algorithm, we retrospectively analyzed the D-dimer, platelet count, prothrombin time, and fibrinogen results for all eligible hospitalized patients (n = 241) who had a D-dimer assay ordered during a 12-month period. A receiver operating characteristic (ROC) curve constructed from the maximum D-dimer measurement for all patients was significant (P < .001) with an area under the curve (AUC) of 0.94. The ROC curves of the other tests were each significant (P < .001), but the AUCs of the prothrombin time (0.74), fibrinogen level (0.70), and platelet count (0.67) did not approach that of the D-dimer. A D-dimer cutoff of 8.2 microg/mL (8,200 microg/L) optimized sensitivity and negative predictive value for the total population and patients with a predisposing condition. Validation against 286 additional patients in a separate analysis verified the diagnostic performance of the aforementioned cutoff. A sensitive, immunoturbidimetric D-dimer assay, by itself provides excellent sensitivity and negative predictive value for the diagnosis of DIC.