Alberto Contador has been banned from professional cycling for two years and had his 2010 Tour de France title stripped.
The 29-year-old Spaniard received the punishment on Monday according to the Spanish Cycling Federation (RFEC) after testing positive for the banned substance clenbuterol.
The decision was made public by the Court of Arbitration for Sport, making Luxembourg's Andy Schleck the retrospective winner of the 2010 Tour.
With Contador's ban dated from when he tested positive in 2010, his suspension will run until August 6 this year.
The ban will rule him out of competing in this year's Tour de France.
Contador has claimed his positive test was a result of eating contaminated meat that contained clenbuterol and his initial hearing – heard by RFEC – cleared him of any wrongdoing.
But an appeal from the World Anti-Doping Agency and Union Cycliste International triggered another investigation, after which Contador has been found guilty.
"This is a sad day for our sport," UCI president Pat McQuaid said.
"Some may think of it as a victory but that is not at all the case. There are no winners when it comes to the issue of doping: every case, irrespective of its characteristics, is always a case too many."
A statement from the UCI added: "In rejecting the defence argument, in particular that the presence of clenbuterol in Alberto Contador's urine sample came from the consumption of contaminated meat, today's ruling confirms the UCI's position."
"However, the UCI has not derived a sense of satisfaction from the CAS ruling, but rather welcomes the news as the end of a long-running affair that has been extremely painful for cycling."