The space shuttle performed a perfect touchdown
ISS commander Frank Culbertson and cosmonauts Vladimir Dezhurov and Mikhail Tyurin returned with "smiles on their faces", according to shuttle commander Dominic Gorie.
"We're very grateful to be home for Christmas," said US astronaut Frank Culbertson shortly after landing.
The shuttle touched down, as planned, at 1255 local time (1755 GMT), despite a delayed departure from the ISS because of concerns about a possible collision with space debris.
The three men were in space during the 11 September attacks.
At the time, they were able to see smoke rising from the burning twin towers from 250 miles (400 kilometres) up as they orbited over North America.
Victims remembered
"That was a horrible thing to see from space, to know that terrible things were happening on Earth like that and we were so far away from our own families," Commander Culbertson said over the weekend.
Last week, the crew of Endeavour and the ISS held a televised memorial service for those who died in the attacks.
And Endeavour has also been carrying thousands of small American flags that will be mounted on certificates and distributed to relatives of the victims, as well as some of those who survived the attacks.
Just like its launch on 5 December, Endeavour's landing was under tight security to protect against any possible terrorist strike.
Four attack helicopters flew in formation over the Kennedy Space Center shortly before touchdown.
Rehabilitation
"We are looking forward to getting home for Christmas, especially Frank and his crew," shuttle commander Dominic Gorie said before landing.
Earlier on Monday, the seven US and Russian astronauts on board Endeavour woke up to the tune Please Come Home For Christmas, by rock group Bon Jovi.
The families of the three returning ISS crew were at the Kennedy Space Center awaiting the spacemen's return.
The three men were strong enough to walk off the shuttle despite spending 129 days in orbit.
But after spending so long in space, they have several weeks of rehabilitation ahead of them.
They will "build up gradually the strength and flexibility and balance skills that have basically been on vacation the last four months", said Nasa flight surgeon Dr Stephen Hart.
The shuttle delivered the new space station crew: Russian Commander Yuri Onufrienko and Americans Daniel Bursch and Carl Walz.
Before leaving the outgoing crew passed on a small fabric Christmas tree and candy canes for their colleagues who are scheduled to remain on the ISS until mid-May.