Television presenter and former pop star Myleene Klass was the special guest as more than 100 specially-selected children embarked on the holiday of a lifetime.
Mother-of-two Klass met children on the Dreamflight charity flight from Heathrow to Orlando in Florida, signing autographs and posing for selfies ahead of the youngsters' ten-day sunshine break.
Gold medallist Paralympians Natasha Baker, David Smith and Sascha Kindred also flew in specially to meet the children.
Previous send-offs have involved celebrities including singer Sir Cliff Richard, presenter Denise van Outen, and Harry Potter actor Matthew Lewis.
The young passengers have been chosen to join the holiday - now in its 30th year - by doctors and medical experts, having battled with serious illness, disability and trauma.
They will visit a host of attractions, including SeaWorld, Disney World and Universal Studios.
Klass said: "It's been an absolute pleasure meeting the children here today. Dreamflight is a unique charity and it's been wonderful to see how excited the kids are to be flying to Florida in style on their own private British Airways' jet."
More than 5,400 children from across the country have been involved in Dreamflight holidays since the first trip in 1987. For many, it has been their first time abroad and also gives them a chance to have a holiday without their family.
The young passengers are accompanied by nearly 100 doctors, nurses and physiotherapists throughout the trip.
The send-off was particularly pertinent for dressage champion Baker, a former Dreamflight child.
She said: "Dreamflight totally changed my life. I went from being such a dependent, shy child to a confident young lady and it's just great to see that it can happen to so many other people."
British Airways comes together with the Dreamflight team each year to make the departure an extra-special event. An army of volunteers, including Darth Vader, his Stormtroopers, the Air Cadet National Marching Band and British Airways' cabin crew and pilots were at Heathrow to see the children board the Boeing 747.
British Airways' senior first officer Rebecca Statham said: "This is my first year flying the Dreamflight aircraft to Florida. The children are such an inspiration to us all, and I feel honoured to be part of the British Airways' team supporting this wonderful once-in-a-lifetime trip."
For more information on Dreamflight, visit dreamflight.org.