Public Health England (PHE) has announced that as little as 3% of winter flu vaccines are estimated to have worked in the current season.
The agency said that a "drift" in the virus has caused a "mismatch" between the influenza strain that was used to create the vaccine and the expected strain that has been doing the rounds this winter, resulting in minimal protection.
It is in stark contrast to the typical 50% effectiveness rate.
John Watson, deputy chief medical officer, said: "We do see 'drift' in the flu virus from time to time, but even so, I want to reassure people that it is still the best overall way to protect yourself and your family from flu, along with good hand hygiene.
"Antiviral drugs are available and effective, and doctors should prescribe them for those at greatest risk of becoming seriously ill due to flu."
Dr Richard Pebody, head of flu surveillance and author of the study from PHE, says that no one can be blamed for the mismatched strain this season as it is almost impossible to predict.
He said: "It's not possible to fully predict the strains that will circulate in any given season, and there is always a risk of a drift occurring as we have seen this year. However, it's important to be aware that this does not occur every season.
"Flu vaccine is still the best protection we have against an unpredictable virus which can cause severe illness and deaths each year among at-risk groups, including older people, pregnant women and those with a health condition, even one that is well managed.
"Throughout the last decade, there has generally been a good match between the strains of flu in the vaccine and those that subsequently circulate, so it's crucial that these results do not discourage people in at-risk groups from having flu vaccination now, or in the future."