To construct a new scoring system utilizing biomarkers, vitals, and imaging data to predict 30-day mortality in acute pulmonary embolism (PE). Acute PE, a well-known manifestation of venous thromboembolic disease, is responsible for over 100,000 deaths worldwide yearly. Contemporary management algorithms rely on a multidisciplinary approach to care via PE response teams (PERT) in the identification of low, intermediate, and high-risk patients. The PESI and sPESI scores have been used as cornerstones of the triage process in assigning risk of 30-day mortality for patients presenting with acute PE; however, the specificity of these scoring systems has often come into question. This study retrospectively analyzed 488 patients with acute PE who were managed at a tertiary care institution with either conservative therapy consisting of low molecular weight or unfractionated heparin, advanced therapies consisting of catheter directed therapies, aspiration thrombectomy, or a combination of these therapies, or surgical embolectomy. The CLOT-5 score was designed to include vital signs, biomarkers, and imaging data to predict 30-day mortality in patients presenting with acute PE. The CLOT-5 score had an area under the curve (AUC) of 0.901 with a standard error of 0.29, while the PESI and sPESI scores had an AUC and standard errors of 0.793 ±- 0.43 and 0.728 ± 0.55, respectively. When incorporated into the management algorithms of national PERT programs, the CLOT-5 score may allow for rapid and comprehensive assessment of patients with acute PE at high risk for clinical decompensation, leading to early escalation of care where appropriate.