The 39-year-old pulled the pin on his professional cycling career on Wednesday and says he will now focus on raising his five children and cancer fundraising ventures.
Armstrong, one of the first major global athletes to make extensive use of the Twitter micro-blogging social messaging website, sent a tweet of thanks Wednesday morning to supporters after making his "retirement 2.0" official.
"Thanks for all the messages on retirement 2.0. and thanks for ALL the support the past 2.5 yrs. Onward!" Armstrong wrote.
Armstrong initially retired from cycling after the 2005 Tour de France, but returned to competition in 2009.
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The American went on to finish third in the 2009 Tour de France and most recently placed 67th in the Tour Down Under in Australia last month.
"My focus now is raising my five children, promoting the mission of (his foundation) Livestrong, and growing entrepreneurial ventures with our great corporate partners in the fight against cancer," Armstrong said.
There were hopes that Armstrong would race in the May 15-22 Tour of California, America's biggest cycling race after changes in the event's drug test program opened the door for him to do so.
But Armstrong's retirement announcement came just hours after he missed the February 15 deadline for putting his name forward for taking part in the Tour of California's random pre-race drug testing program being administered by the US Anti-Doping Agency (USADA).
Armstrong is the subject of a federal investigation in the United States after allegations of doping levelled by disgraced former teammate Floyd Landis, who was stripped of his 2006 Tour de France title for using illegal substances.
But Armstrong, who was diagnosed with testicular cancer at the age of 25, has never tested positive for performance-enhancing drugs and has consistently denied allegations of doping, notably from French authorities.
Armstrong's tweets also revealed he enjoyed dinner on his last day as a pro cyclist at a French restaurant.
"Dinner tonight at Texas French Bread was amazing. 1st time there and glad we ventured out. BYOB too. Or BYOW in our case," Armstrong tweeted.
Seven-time Tour de France winner Lance Armstrong has tweeted a message of thanks to his army of supporters after announcing his retirement.
