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Background: Pulmonary emboli (PE) are obstructions in the pulmonary arteries causing reduced alveolar perfusion. They remain a significant treatment challenge in acute medicine. They are a significant cause of patient mortality, particularly high-risk PE, which can present with hemodynamic instability and have documented 30-day mortality rates as high as 25 percent. Therefore, it is imperative to be able to promptly recognize and treat patients with high-risk PE. The treatment landscape of PE has evolved significantly, and continues to do so, especially given the advancement of catheter-directed therapies. Herein, we explore the current best practices for the diagnosis and treatment of high-risk PE, with a focus on pathophysiology, risk stratification, and the latest advancements in diagnosis and treatment. Additionally, we discuss the comparative evidence between treatment strategies in high-risk PE, including the …