Purpose: To present the outcomes of large-bore mechanical thrombectomy (LBMT) for acute pulmonary embolism (PE) from the combined US and European cohorts of the FLASH study. Methodology: FLASH (NCT03761173) prospectively enrolled real-world subjects treated with the FlowTriever system (Inari, Irvine, CA, US) for intermediate-risk or high-risk PE. The composite primary endpoint consisted of independently adjudicated major adverse events (AEs) comprising major bleeding and device-related mortality through 48 hours and intraprocedural device-related or procedure-related AEs. Severe dyspnea was defined as a modified Medical Research Council score of 3 or 4. Subjects were followed for 6 months. Results: The analysis population included 999 subjects enrolled across 69 sites. Mean age was 61.6±14.3 years, and 453 (45.3%) subjects were female. The stratification by PE risk was 14.3% high risk, 72.0% intermediate-high risk, 6.5% intermediate-low risk, and 7.1% intermediate risk without further classification. Immediately after thrombectomy, mean pulmonary artery pressure improved from 32.6±8.8 to 25.0±8.6 mmHg (-22.7% for paired values, P<.0001). Thrombectomy time was 49.8±35.4 minutes, and adjunctive therapy was used in 22 (2.2%) cases. Twenty-four (2.4%) subjects met the primary endpoint, 0 with device-related mortalities, 17 (1.7%) with major bleeds, and 8 (0.8%) with intraprocedural AEs related to the device or procedure. All-cause mortality rates at 48 hours, 30 days, and study exit were 0.6%, 1.8%, and 5.6%, respectively. The proportion of subjects with severe dyspnea improved from 70.9% at baseline to 16.2% (P<.0001) at the 48-hour visit and continued improving to 3.0% (P<.0001) at the 6-month visit. There were low rates of chronic thromboembolic pulmonary hypertension (1.2%) and post-PE syndrome (1.9%) at 6-month follow-up. Conclusion: Data from the FLASH study of acute PE indicate that LBMT is safe and associated with favorable acute and long-term outcomes.