We analyze here data from the Italian coronavirus disease 2019 (COVID-19) vaccination campaign for providing real-world evidence on age-dependent efficacy of vaccination. Vaccine efficacy against infection, COVID-19 related hospitalization and intensive care unit (ICU) admission increased according to vaccination status, from people who received primary COVID-19 vaccination >4 months ago (36%, 87% and 93%, respectively), to those who received primary COVID-19 vaccination <4 months ago (60%, 90% and 94%, respectively), and finally to those with booster vaccine dose (60%, 98% and 98%, respectively). Vaccine efficacy (both primary and booster) against SARS-CoV-2 infection increased with ageing, though a similar trend could not be observed for hospitalization or ICU admission. Booster vaccine doses generated adjunctive protection against all endpoints compared to early primary vaccination in older people (i.e., aged >60 years). In conclusion, vaccine-elicited SARS-CoV-2 immunity declines over time, though vaccine boosters are effective for restoring immunity and conferring adjunctive protection.