Background: Adherence to guidelines by physicians of an emergency department (ED) depends on many factors: guideline and environmental factors; patient and practitioner characteristics; the social-political context. We focused on the impact of the environmental influence and of the patients’ characteristics on adherence to the guidelines. It is our intention to demonstrate how environmental factors such as ED organization more affect adherence to guidelines than the patient’s clinical presentation, even in a clinically insidious disease such as pulmonary embolism (PE). Methods: A single-center observational study was carried out on all patients who were seen at our Department of Emergency and Acceptance from 1 January to 31 December 2017 for PE. For the assessment of adherence to guidelines, we used the European guidelines 2014 and analyzed adherence to the correct use of clinical decision rule (CDR as Wells, Geneva, and YEARS); the correct initiation of heparin therapy; and the management of patients at high risk for short-term mortality. The primary endpoint of our study was to determine whether adherence to the guidelines as a whole depends on patients’ management in a holding area. The secondary objective was to determine whether adherence to the guidelines depended on patient characteristics such as the presence of typical symptoms or severe clinical features (massive pulmonary embolism; organ damage). Results: There were significant differences between patients who passed through OBI and those who did not, in terms of both administration of heparin therapy alone (p = 0.007) and the composite endpoints of heparin therapy initiation and observation/monitoring (p = 0.004), as indicated by the guidelines. For the subgroups of patients with massive PE, organ damage, and typical symptoms, there was no greater adherence to the decision making, administration of heparin therapy alone, and the endpoints of heparin therapy initiation and guideline-based observation/monitoring. Conclusions: Patients managed in an ED holding area were managed more in accordance with the guidelines than those who were managed only in the visiting ED rooms and directly hospitalized from there.