In the Emergency Department (ED), the decision to hospitalize or discharge COVID-19 patients is challenging. We assessed the utility of lung ultrasound (LUS), alone or in association with a clinical rule/score. This was a multicenter observational prospective study involving six EDs (NCT046291831). From October 2020 to January 2021, COVID-19 outpatients discharged from the ED based on clinical judgment were subjected to LUS and followed-up at 30 days. The primary clinical outcome was a composite of hospitalization or death. Within 393 COVID-19 patients, 35 (8.9%) reached the primary outcome. For outcome prognostication, LUS had a C-index of 0.76 (95%CI 0.68–0.84) and showed good performance and calibration. LUS-based classification provided significant differences in Kaplan–Meier curves, with a positive LUS leading to a hazard ratio of 4.33 (95%CI 1.95–9.61) for the primary outcome. The sensitivity and specificity of LUS for primary outcome occurrence were 74.3% (95%CI 59.8–88.8) and 74% (95%CI 69.5–78.6), respectively. The integration of LUS with a clinical score further increased sensitivity. In patients with a negative LUS, the primary outcome occurred in nine (3.3%) patients (p < 0.001 vs. unselected). The efficiency for rule-out was 69.7%. In unvaccinated ED patients with COVID-19, LUS improves prognostic stratification over clinical judgment alone and may support standardized disposition decisions.