Advanced D-dimer (Dade Behring, Marburg, Germany) is a latex-enhanced turbidimetric test for the quantitative determination of D-dimers. To evaluate this assay, examine test performance on 2 instruments (BCS Analyzer and Sysmex CA-1500, Dade Behring), establish negative predictive value cutoffs (NPVCs), and compare the test with the qualitative SimpliRed test (Agen Biomedical, Brisbane, Australia), we evaluated 117 patients for possible acute thromboembolic disease (pulmonary embolus or deep venous thrombosis). Patients selected for the study were those with confirmatory tests (ultrasound, spiral computed tomography, ventilation-perfusion scan, or angiography) and those without certain medical conditions that might be associated with increased D-dimers. An NPVC of 1.8 mg/L for the BCS Analyzer resulted in 41.0% negative results (48/117) and sensitivity, specificity, and negative and positive predictive values of 100%, 48%, 100%, and 21%, respectively. An NPVC of 1.1 mg/L for the Sysmex CA-1500 resulted in 31.6% negative results (37/117) and sensitivity, specificity, and negative and positive predictive values of 100%, 36%, 100%, and 18%, respectively. The SimpliRed had 31.6% negative results (37/117) and sensitivity, specificity, and negative and positive predictive values of 86%, 34%, 96%, and 15%, respectively.