Some legal experts believe the disillusionment and anger now directed at Armstrong will force the government to re-examine its evidence in light of his admissions, but others say revisiting the criminal case is unlikely.
"There are no formal guidelines on reopening one, and the discretion is left to the prosecutor," said Matthew Levine, a former federal prosecutor and a white-collar defense attorney in New York. "But generally there's a lot of pressure not to reopen, especially where the declination has been made public. It does happen, but it's quite rare."
Last February, federal prosecutors in Los Angeles announced they were dropping their investigation into Armstrong. A federal grand jury heard testimony from the cyclist's former teammates and associates that could have helped prove Armstrong and some of his fellow cyclists violated federal conspiracy, fraud or racketeering charges.
No reason was given for the decision. Thom Mrozek, a spokesman for the U.S. attorney's office, declined comment Friday.
In the portion of his interview with Winfrey that aired Thursday, Armstrong refused to implicate anyone else. Winfrey asked Armstrong if he felt victorious when the government declined to file charges against him.
"It's hard to define victory," Armstrong said. "But I thought I was out of the woods."
Unlike fellow sports superstars such as Barry Bonds and Roger Clemens who faced criminal charges, Armstrong never spoke with federal authorities or testified before Congress, either or which could have led to obstruction or making false statements charges.
Clemens was acquitted last year on six counts that he lied and obstructed Congress when he denied using performance-enhancing drugs. Bonds was found guilty of obstruction of justice in December 2011 and sentenced to 30 days' home detention. His case is under appeal.
Peter Keane, a law professor at Golden Gate University in San Francisco, is convinced the criminal case will be reopened.
Because of a fraud, "he became very famous, very rich," Keane said. "The idea of him getting a pass on it is going to be looked at with a degree of there's a double standard here. It's something (the government) takes very seriously and they want to discourage people from doing it."
If prosecutors try reopening the case, they do face a hurdle, possibly one that hampered the initial investigation. Any charges may have fallen outside the statute of limitations, but some legal observers said there may be some wiggle room.
"On the criminal side, there are certainly timing issues, but I've never met a prosecutor who didn't try to find a creative way around a statute of limitations," said Marc Mukasey, also a former federal prosecutor and New York-based defense attorney.
Most legal experts agree, however, that Armstrong's confession will expose him to various lawsuits. He is worth an estimated $100 million.
Already, the London-based Sunday Times has filed a suit to recoup about $500,000 it paid Armstrong to settle a libel case. Dallas-based SCA Promotions, which tried to deny Armstrong a bonus it promised for a Tour de France win, has threatened to bring another lawsuit seeking to recover more than $7.5 million awarded by an arbitration panel.
Most damaging could be a whistleblower lawsuit against Armstrong by former teammate Floyd Landis, who claims the seven-time Tour de France winner defrauded the U.S. government by repeatedly denying he used performance-enhancing drugs.
The suit could require Armstrong to return substantial sponsorship fees and pay a hefty fine.
Justice Department officials were likely to join the suit, an attorney who works outside the government told The Associated Press earlier this week. The person requested anonymity because he was not authorized to speak on the record about the matter.
Levine, the former federal prosecutor, said Armstrong's lawyers would likely push for a "non-prosecution" agreement in settlement talks, one that essentially promises the government won't ever charge the cyclist in connection with the doping probe.
A potential deal also may require Armstrong to provide details about those who were running the doping program, but any revelation might not go very far, Levine said.
"Even if they do get him to cooperate, he's damaged goods," Levine said. "Who is going to believe this guy?"