Abstract Introduction In spite of a multitude of innovative therapeutic strategies emerging in the past decade, acute pulmonary embolism (PE) remains a potentially fatal disease. However, mortality varies significantly according to risk stratification, substantiating current recommendations to use reperfusion therapy only in hemodynamically unstable patients. There is an ongoing debate around whether hemodynamically stable patients showing signs of right ventricle dysfunction and myocardial injury (intermediate-high risk acute PE) may also benefit from reperfusion therapy. While the majority of patients in this category typically improve with anticoagulation alone, up to 10% may experience clinical deterioration. Aim We aimed to characterize the clinical in-hospital progression of patients with intermediate-risk PE and to evaluate the discriminative efficacy of PE scores in anticipating unfavorable clinical outcomes. Methods We conducted a retrospective observational study in patients admitted with the diagnosis of PE classified as intermediate risk in a tertiary center. Clinical, laboratory and ECG data were obtained. The BOVA score, the News score and the Pope score were evaluated. A composite endpoint of in-hospital mortality and use of reperfusion therapy due to hemodynamic deterioration was defined. Predictive abilities of these three scores were compared using area under the receiver operating characteristics (AUC-ROC) curve. Results From January 2019 to December 2020, a total of 166 patients were admitted with acute PE, classified as intermediate-risk, in our center. The mean age 71.9 ± 16.2 years and 57.2% were female. 71.1% of the pts showed bilateral PE in chest CT. The composite endpoint of in-hospital mortality and reperfusion therapy due to hemodynamic deterioration occurred in 9.8% of the pts. The median BOVA score was 3 (2-4), the median POPE score was 1 (0-2) and the median News score was 4 (2-6). The ROC curve analysis showed a significant higher discriminative power of POPE score compared to the other scores (AUC 0.856 95%CI 0.79–.92, p<0.001) (Fig1). Compared to patients with a POPE score 1, the composite endpoint was 4,6 times higher in patients with higher scores (OR 4.6 95%CI 1.63- 6914, p=0.029) (Fig2). Conclusion Despite classification as intermediate risk, these patients displayed a non-negligible in-hospital mortality rate. Close clinical monitoring is warranted in this group of pts and there is pressing need for an early identification of those who might benefit from more than just anticoagulation. In our population POPE score showed to be a simple and accurate tool in predicting those with an unfavorable evolution that could have benefitted from more advanced intervention.