BACKGROUND: The ability of various D-dimer assays to exclude the diagnosis of thromboembolic diseases is controversial. We examined the diagnostic accuracy of two D-dimer methods in hospitalized patients and outpatients. METHODS: We studied consecutive patients for whom D-dimer testing was ordered for investigation of suspected pulmonary embolism. We measured D-dimer by an ELISA (VIDAS D-dimer) and an enhanced microlatex immunoassay method (Diagnostica Stago STA Liatest D-di). Patient diagnoses were based on imaging studies or, when these were not performed, on follow-up by review of medical records 3 months later. RESULTS: We examined 233 hospitalized patients and 234 outpatients with a mean age of 58 years (range, 1-92 years) and a female-to-male ratio of 1.4 to 1. Thromboembolism was present in 8% of outpatients and 12% of hospitalized patients. In outpatients, the negative predictive values were 98% [95% confidence interval (CI), 93-100%] and 99% (94-100%) for the microlatex and ELISA methods, respectively, at the recommended cutoffs. Areas under the ROC curves were similar for the two methods [0.77 (95% CI, 0.67-0.87) and 0.81 (0.73-0.89), respectively]. By contrast, in hospitalized patients, the confidence intervals for the areas under the ROC curves included 0.5 [0.60 (95% CI, 0.50-0.71) and 0.56 (0.44-0.67)]. CONCLUSIONS: For hospitalized patients, in contrast to outpatients, the diagnostic accuracy of D-dimer testing for pulmonary embolism is poor in a tertiary care setting, presumably reflecting thrombosis and comorbidities, other than pulmonary embolism, that increase the D-dimer concentrations in these patients. The patient population studied appears more important than assay method in studies of the diagnostic accuracy of D-dimer testing.