Patients who present to the emergency department (ED) for suspected pulmonary embolism (PE) are often on active oral anticoagulation (AC). However, the diagnostic yield of computed tomography pulmonary angiography (CTPA) in screening for PE in patients who present on AC has not been well characterized. We aim to investigate the diagnostic yield of CTPA in diagnosing PE depending on AC status. We reviewed and analyzed the electronic medical records of patients who underwent CTPA for PE at a university hospital ED from June 1, 2019, to March 25, 2022. Primary outcome was the incidence of PE on CTPA depending on baseline AC status and indication for AC. Of 2,846 patients, 242 were on AC for a history of venous thromboembolism (VTE), 210 were on AC for other indications, and 2,394 were not on AC. The incidence of PE on CTPA was significantly lower in patients on AC for other indications (5.7%) when compared to patients on AC for prior VTE (24.3%) and patients not on AC at presentation (9.8%) (P<0.001). In multivariable analysis among the whole cohort, AC was associated with a positive CTPA (odds ratio [OR] 0.26, 95% confidence interval [CI]: 0.15-0.45, P<0.001). The incidence of PE among patients undergoing CTPA in the ED is lower in patients previously on AC for indications other than VTE when compared to those not on AC or those on AC for history of VTE. AC status and indication for AC may affect pre-test probability of a positive CTPA, and AC status therefore warrants consideration as part of future diagnostic algorithms among patients with suspected PE.