Purpose To determine the frequency of, and yield after, provider overrides of evidence-based clinical decision support (CDS) for ordering computed tomographic (CT) pulmonary angiography in the emergency department (ED). Materials and Methods This HIPAA-compliant, institutional review board-approved study was performed at a tertiary care, academic medical center ED with approximately 60 000 annual visits and included all patients who were suspected of having pulmonary embolism (PE) and who underwent CT pulmonary angiography between January 1, 2011, and August 31, 2013. The requirement to obtain informed consent was waived. Each CT order for pulmonary angiography was exposed to CDS on the basis of the Wells criteria. For patients with a Wells score of 4 or less, CDS alerts suggested d-dimer testing because acute PE is highly unlikely in these patients if d-dimer levels are normal. The yield of CT pulmonary angiography (number of positive PE diagnoses/total number of CT pulmonary angiographic examinations) was compared in patients in whom providers overrode CDS alerts (by performing CT pulmonary angiography in patients with a Wells score ≤4 and a normal d-dimer level or no d-dimer testing) (override group) and those in whom providers followed Wells criteria (CT pulmonary angiography only in patients with Wells score >4 or ≤4 with elevated d-dimer level) (adherent group). A validated natural language processing tool identified positive PE diagnoses, with subsegmental and/or indeterminate diagnoses removed by means of chart review. Statistical analysis was performed with the χ2 test, the Student t test, and logistic regression. Results Among 2993 CT pulmonary angiography studies in 2655 patients, 563 examinations had a Wells score of 4 or less but did not undergo d-dimer testing and 26 had a Wells score of 4 or less and had normal d-dimer levels. The yield of CT pulmonary angiography was 4.2% in the override group (25 of 589 studies, none with a normal d-dimer level) and 11.2% in the adherent group (270 of 2404 studies) (P < .001). After adjustment for the risk factor differences between the two groups, the odds of an acute PE finding were 51.3% lower when providers overrode alerts than when they followed CDS guidelines. Comparison of the two groups including only patients unlikely to have PE led to similar results. Conclusion The odds of an acute PE finding in the ED when providers adhered to evidence presented in CDS were nearly double those seen when providers overrode CDS alerts. Most overrides were due to the lack of d-dimer testing in patients unlikely to have PE. © RSNA, 2016.