The randomized, controlled study published in the New England Journal of Medicine is the first of its kind to measure how well the flu shot works specifically in children.
Experts said the findings should sway those who question whether the shot is worthwhile, since the flu can lead to deadly complications, particularly among the young and those with weakened immune systems.
The US Centers for Disease Control and Prevention recommends the flu vaccine for all people aged six months and over, but just under 37 percent of Americans received it last year.
Both vaccines were made by the British pharmaceutical giant GlaxoSmithKline, which funded the research.
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The study was carried out at 15 sites in Bangladesh, the Dominican Republic, Honduras, Lebanon, Panama, the Philippines, Thailand and Turkey.
The flu shot was effective 59.3 per cent of the time at preventing influenza A or B, observed via common flu symptoms and confirmed in laboratory tests.
And when researchers looked at how the flu shot worked at fending off harsher cases of sickness, such as pneumonia, brain swelling and seizures, they found an efficacy rate of 74.2 per cent.
"Influenza vaccine should be looked at with that perspective. Vaccines that prevent death are of value," said Bromberg, who was not involved in the study.
Researchers found that the flu vaccine, when compared to the control shot, also was associated with "69 per cent fewer medical visits, 75 per cent fewer hospitalizations, 77 per cent fewer absences from school and 61 per cent fewer parental absences from work."
Until now, there had been no large research study that showed how well the quadrivalent flu vaccine worked at preventing illness in children.
"This study adds important information to our body of knowledge on prevention of childhood influenza," said Sunil Sood, chairman of pediatrics at Southside Hospital in Bay Shore, New York, who was not involved in the research.
It "bolsters the national recommendation to vaccinate every child six months and older every year against influenza.