It was the objective of this study to determine the proportion of patients who undergo an appropriate diagnostic work-up following a D-dimer test performed to evaluate suspected pulmonary embolism (PE) or deep vein thrombosis (DVT). We performed a retrospective cohort study at a tertiary care hospital. We included patients if they underwent D-dimer testing between 2002 and 2005, if the D-dimer was performed for evaluation of VTE, and if the D-dimer test was successful. We classified: the patients' clinical probability of DVT or PE according to the Wells models, the imaging results, and the appropriateness of the testing algorithm. Of 1,000 randomly selected patients, 863 met our study criteria. Seven hundred nineteen patients (83%) had testing during an emergency department visit, while 144 were tested as inpatients (17%). Physicians performed the D-dimer test to evaluate DVT and PE in 238 (28%) and 625 (72%) patients, respectively. Overall, the testing strategy was appropriate in 69% (95% confidence interval [CI]: 66%-72%) of cases. The testing strategy was more likely to be appropriate for emergency department versus inpatients (75% vs. 39%, p < 0.05) and for DVT versus PE patients (84% vs. 63%, p < 0.05). Of all in-appropriately tested patients, under-utilization of diagnostic imaging was more common than over-utilization (90% vs. 10%, p < 0.05). VTE was confirmed in 37 of 138 'DVT patients' and 35 of 625 'PE patients' (16% [95% CI: 11%-21%] and 6% [95% CI: 4%-8%], respectively). In conclusion, physicians often fail to use diagnostic testing strategies for VTE correctly following a D-dimer test.