Armstrong told Winfrey he used banned substances and blood transfusions in all of his Tour de France wins, calling it "one big lie" that became too big to sustain.
Armstrong, stripped of his seven Tour titles last year after the U.S. Anti-Doping Agency determined he led "the most sophisticated, professionalized and successful doping program that sport has ever seen," admitted to using erythropoietin, cortisone, testosterone, human growth hormone and other banned drugs.
He told Winfrey he didn't believe it would have been "humanly possible" to achieve his success without cheating, but he believed he was operating on a "level playing field."
Betsy Andreu, wife of former Armstrong teammate Frankie Andreu, told CNN she expected more from the interview.
Armstrong attacked the couple after she said she had heard him admitting to doctors treating him for cancer that he had taken drugs to enhance his racing performance.
"This was a guy who used to be my friend, who decimated me," Andreu said. "He could have come clean. He owed it to me. He owes it to the sport that he destroyed."
Scott Allison, a University of Richmond professor who has studied heroes who have fallen from grace, compared Armstrong to another sports idol, the Los Angeles Times reported.
"It kind of reminded me of Tiger Woods coming clean," Allison said. "For people like Tiger Woods and Lance Armstrong, it's so foreign to admit wrongdoing that they are out of their element. ... It can come across as robotic."
Christine Brennan, an ABC News consultant who writes a column for USA Today, said Armstrong may have done the Winfrey interview too soon.
"It was a lose-lose going in. I think he did more harm than good to his reputation, and he just looked cold-blooded and cutthroat, and ruthless," Brennan said on ABC's "Good Morning America."
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