In the first part of the interview, Armstrong finally admitted to what the sporting world had suspected for years - that the Texan had cheated his way to a record seven Tour de France titles.
Armstrong evaded many of the questions asked by Winfrey and was heavily criticised for showing little contrition, but those who know him said that was typical of his character.
"He's never been one to be super apologetic," his former team-mate, Tyler Hamilton, told CNN.
"I don't ever think he apologised back in the day when we were team-mates for a whole lot of anything, really.
"He doesn't show a lot of emotion. Last night I did see - for Lance Armstrong - quite a bit of emotion ... by his standards."
Hamilton was one of the riders who helped bring down Armstrong, providing sworn evidence to the United States Anti-Doping Agency that Armstrong used banned substances.
Hamilton also confessed to cheating and was subsequently stripped of the gold medal he won at the 2004 Athens Olympics.
He said he felt vindicated by Armstrong's admission.
"It's nice to hear him finally own up to some of his faults," he said.
But Hamilton said Armstrong had not been completely honest and needed to reveal more, a sentiment that was echoed across the sporting world.
World Anti-Doping Agency chief John Fahey said Armstrong had lied in the interview when he said he stopped doping after 2005 when he won his seventh Tour de France.
Armstrong retired after the race before making a comeback in 2009 but said he raced clean in his return.
"The evidence from USADA is that Armstrong's blood tests show variations in his blood that show with absolute certainty he was doping after 2005," Fahey told the Daily Telegraph.
"Believe USADA or believe Armstrong? I know who to believe."
Another newspaper, the Sunday Times, said it would vigorously pursue a £1 million legal action against Armstrong following his admission.
The Sunday Times paid Armstrong in 2006 to settle a legal case after it had questioned what was behind his Tour de France wins in an article published in 2004.
The newspaper, part of Rupert Murdoch's media business, also wants to recover interest and legal costs incurred in the case.
"We watched Lance Armstrong's interview with interest and noted his numerous admissions regarding taking performance-enhancing drugs," a Sunday Times spokesman said.
"The Sunday Times believes that our case for recovering the £1 million he obtained from us by fraud is now even stronger. We will be pursuing that case vigorously."
A lawyer for SCA Promotions, a Dallas-based insurance company, said it would take legal action against Armstrong unless he repaid them more than $12 million they gave him for his Tour de France wins.
Tillotson said the company would make a decision on the lawsuit after watching Friday's second and final part of the interview.
"No one should underestimate the resolve of SCA," Jeff Tillotson told Reuters. "If it doesn't get back its money, SCA will sue Mr. Armstrong for the refund of that money, and it will be soon."
The International Olympic Committee, which announced on Thursday that it had stripped Armstrong of the bronze medal he won at the Sydney 2000 Games, said Armstrong had done nothing to redeem himself in the first part of the interview.
"If Lance Armstrong believes he can win credibility with this interview then it is too little, too late," IOC Vice-President Thomas Bach told Reuters.
"There are no new facts or evidence related to the USADA report in the entire interview. It was clearly a well-orchestrated interview which, however, did provide no new facts."
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