DescriptionObjective. To evaluate the usability and use of a human factors (HF)-based clinical decision support (CDS) implemented in the emergency department (ED). Background. CDS can improve patient safety; however, the acceptance and use of CDS has faced challenges. Following a human-centered design (HCD) process, we designed a CDS to support pulmonary embolism (PE) diagnosis in the ED. We demonstrated high usability of the CDS during scenario-based usability testing. We implemented the HF-based CDS in one ED in December 2018. Method. We conducted a survey of ED physicians to evaluate the usability and use of the HF-based CDS. We distributed the survey via Qualtrics, a web-based survey platform. We compared the computer system usability questionnaire (CSUQ) scores of the CDS between those collected in the usability testing to use of the CDS in the real environment. We asked physicians about their acceptance and use of the CDS, barriers to using the CDS, and areas for improvement. Results. Forty-seven physicians (56%) completed the survey. Physicians agreed that diagnosing PE is a major problem and risk scores can support the PE diagnostic process. Usability of the CDS was reported as high, both in the experimental setting and the real clinical setting. However, use of the CDS was low. We identified several barriers to the CDS use in the clinical environment, in particular a lack of workflow integration. Conclusion. Design of CDS should be a continuous process and focus on the technology’s usability in the context of the broad work system and clinician workflow.