Background: Since data on the safety and effectiveness of home telemonitoring and oxygen therapy started directly after Emergency Department (ED) assessment in COVID-19 patients are sparse but could have many advantages, we evaluated these parameters in this study. Methods: All COVID-19 patients ≥18 years eligible for receiving home telemonitoring (November 2020-February 2022, Albert Schweitzer hospital, the Netherlands) were included: patients started directly after ED assessment (ED group) or after hospital admission (admission group). Safety (number of ED reassessments and hospital readmissions) and effectiveness (number of phone calls, duration of oxygen usage and home telemonitoring) were described in both groups. Results: 278 patients were included (n = 65 ED group, n = 213 admission group). ED group: 23.8% (n = 15) was reassessed, 15.9% (n = 10) was admitted and 7.7% (n = 5) ICU admitted. Admission group: 15.8% (n = 37) was reassessed, 6.5% (n = 14) was readmitted and 2.4% (n = 5) ICU (re)admitted. Ten patients died, of whom 7 due to COVID-19 (1 in ED group; 6 in the admission group). ED group: median duration of oxygen therapy was 9 (IQR 7–13) days; the total duration of home telemonitoring was 14 (IQR 9–18) days. Admission group: duration of oxygen therapy was 10 (IQR 6–16) days; total duration of home telemonitoring was 14 (IQR 10–20) days. Conclusion: it appears to be safe to start home telemonitoring and oxygen therapy directly after ED assessment.