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Long–term clinical follow–ups are needed to assess the effectiveness of vaccine and booster doses against severe acute respiratory syndrome coronavirus 2 (SARS–CoV2) infection for heart transplant (HT) recipients, particularly in an epidemiological landscape characterized by rapidly changing viral variants. Among patients who received HT at Niguarda Hospital from January 2008 to March 2022, we compared the clinical outcomes of those who developed SARS–CoV2 infection between March 2020 and January 2023, according to their vaccination status (vaccinated Vs unvaccinated). Of 377 patients, 98 (25,9%) developed SARS–CoV2 infection during the study period. 24 (27.5 %) developed infection before receiving the vaccination, whilst 74 (75,5%) almost after 2 weeks from receiving the first dose. The unvaccinated cohort demonstrated a higher incidence of death, pneumonia, requiring of oxygen supplementation, non–invasive and invasive ventilation therapy. Furthermore, we assess an additional protective effect against mortality offered from booster doses. Vaccine administration in HT patients is associated with a lower rate of death and severe disease, particularly in those patients who received one or two booster doses.