The Home Treatment of Pulmonary Embolism (HoT-PE) prospective multicenter single-arm phase 4 trial investigated the early discharge of patients with low-risk pulmonary embolism followed by three-month ambulatory treatment with rivaroxaban. The primary efficacy outcome was three-month symptomatic recurrent venous thromboembolism. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. In the trial population (576 patients), the primary efficacy outcome occurred in three (0.5%, one-sided upper 95% CI 1.3%) patients. The median length of hospitalization was 33 (Q1-Q3: 23-47) hours. The 1-year mortality was 2.4%. Six (1.1%) patients had major bleeding. The mean disease-specific quality of life (based on the Pulmonary Embolism Quality of Life questionnaire; PEmb-QoL) improved from 28.9±20.6% at 3 weeks to 19.9±15.4% at 3 months (mean change of -9.1%; p<0.0001). Generic quality of life (based on the five-level five-dimension EuroQoL questionnaire; EQ-5D-5L) improved from 0.89±0.12 at 3 weeks to 0.91±0.12 at 3 months (p<0.0001). Female sex and cardiopulmonary disease were associated with poorer disease-specific and generic quality of life; older age was associated with faster worsening of generic quality of life. Our results further support early discharge and ambulatory oral anticoagulation for selected patients with low-risk pulmonary embolism. Targeted strategies may be necessary to further improve quality of life in specific patient subgroups.