The prevalence of venous thromboembolism (VTE) in COVID-19 patients is highly variable, depending on methodological and clinical factors, among which vaccination (1). The hypothesis of a possible protective role of vaccination in preventing pulmonary embolism (PE) in hospitalized COVID-19 patients has not been explored. The aim of the study was to evaluate PE prevalence in vaccinated versus unvaccinated hospitalized COVID-19 patients. We conducted a retrospective case–control study from 2021/11/01 to 2022/01/15; we reviewed all the chest computed topographies (chest-CT) performed because of a clinical suspicion for PE at our Institution. Sixty-two patients were included in the study: 27/62 (43.5%) were vaccinated and 35/62 (56.4%) were not. Vaccinated patients were older and with more comorbidities than unvaccinated people. Overall, PE was diagnosed in 19/62 patients (30.1% prevalence). CT Severity Score (CT-SS) differs between the two groups; not vaccinated patients had a more severe CT imaging than the vaccinated (< 0.00005). PE prevalence in ICU was 43.2% (16/37 patients), while in the Internal Medicine ward, it was 12% (3/25 cases). PE was significantly higher among unvaccinated people: 16/35 (45.7%) vs 3/27 (11.1%), ORp= 0.04. We observed a strong association between vaccination and protection from PE in hospitalized COVID-19 patients: morbidity was significantly lower in vaccinated versus not vaccinated patients. The issue of the protective role of vaccination in COVID-19-associated VTE should be addressed in adequately designed and powered future prospective studies.