COVID-19 vaccines have proven very successful in protecting against severe disease. However, they only provide partial protection against infection, and an increasing number of individuals suffer breakthrough infections (BTIs) after vaccination. Al-Aly and colleagues investigated the vast US department of Veterans Affairs national health-care database to determine the level of protection vaccines provide against post-acute COVID-19 sequelae (‘Long COVID’). They found that individuals with BTIs, compared with unvaccinated individuals, had a lower risk of death and Long COVID between of 1–6 months post-infection, particularly when comparing patients who had been hospitalized with COVID-19. However, the overall protection of the vaccine from Long COVID was only ~15%, which means that the burden of Long COVID is likely to be substantial even in fully vaccinated populations. Therefore, vaccination alone may not be enough to mitigate the long-term health consequences of SARS-CoV-2 infection.