ABSTRACT: To determine the effect of evidence-based clinical decision support (CDS) on the use and yield of computed tomographic (CT) pulmonary angiography for acute pulmonary embolism (PE) in the emergency department (ED).Institutional review board approval was obtained for this HIPAA-compliant study, which was performed between October 1, 2003, and September 30, 2009, at a 793-bed quaternary care institution with 60,000 annual ED visits. Use (number of examinations per 1000 ED visits) and yield (percentage of examinations positive for acute PE) of CT pulmonary angiography were compared before and after CDS implementation in August 2007. The authors included all adult patients presenting to the ED and developed and validated a natural language processing tool to identify acute PE diagnoses. Linear trend analysis was used to assess for variation in CT pulmonary angiography use. Logistic regression was used to determine variation in yield after controlling for patient demographic and clinical characteristics.Of 338,230 patients presenting to the ED, 6838 (2.0%) underwent CT pulmonary angiography. Quarterly CT pulmonary angiography use increased 82.1% before CDS implementation, from 14.5 to 26.4 examinations per 1000 patients (P<.0001) between October 10, 2003, and July 31, 2007. After CDS implementation, quarterly use decreased 20.1%, from 26.4 to 21.1 examinations per 1000 patients between August 1, 2007, and September 30, 2009 (P=.0379). Overall, 686 (10.0%) of the CT pulmonary angiographic examinations performed during the 6-year period were positive for PE; subsequent to CDS implementation, yield by quarter increased 69.0%, from 5.8% to 9.8% (P=.0323).Implementation of evidence-based CDS in the ED was associated with a significant decrease in use, and increase in yield, of CT pulmonary angiography for the evaluation of acute PE.