Mr Uribe's second term has been hit by scandals but he remains popular
The Colombian constitutional court has rejected a referendum which could have led to President Alvaro Uribe running for a third term in office.
The court voted 7-2 against a proposal backed by parliament to hold a vote on amending the constitution to allow for three terms.
Mr Uribe won an amendment in 2005 that let him run for a second term in 2006.
Following the ruling, former Defence Minister Juan Manuel Santos confirmed he would run for the presidency.
Mr Santos, credited with helping Mr Uribe's government's efforts against left-wing Farc rebels, said: "What we need to do now is work to ensure his [Mr Uribe's] legacy of security and progress is not lost."
President Uribe remains popular in Colombia, but the constitution bars him from being a candidate again in the 30 May election.
He said he accepted and respected the court's decision, which is not subject to appeal.
Alvaro Uribe is a close ally of the US, which has poured many millions of dollars into Colombia to support its fight against drug cartels and the Farc insurgency.
Last year, Colombia's Senate and House of Representatives overwhelmingly backed the proposed amendment on term limits.
But on Friday, lead justice Mauricio Gonzalez announced that the high court rejected the referendum that would have asked voters to amend the constitution.
In his ruling he said the law calling for such a referendum included "substantial violations to the democratic principle."
"It is not a matter of mere... irregularities," he added.
Analysts say the court ruling marks the start of a tough election campaign to replace Mr Uribe.
Mr Santos leads in opinion polls, reports say, but Sergio Fajardo, an independent praised for his performance as mayor of Medellin, is making ground.
Correspondents say that any candidate chosen to replace the president from among his allies would continue his Democratic Security Policy, the foundation of his popularity.
"Those policies have to be re-elected whatever the decision of the court," Mr Uribe said on Thursday evening.
"We cannot change direction, we cannot have a change of guard."
Critics have said that allowing Mr Uribe to stand again might threaten democracy.
His second term has been marred by scandals over human rights abuses by troops and the illegal wiretapping of his opponents by the state intelligence agency.
On Wednesday, police re-arrested a cousin and close ally of the president, former senator Mario Uribe Escobar, as part of an ongoing investigation into alleged links between politicians and right-wing paramilitary groups.
More than 60 politicians are still in jail in connection with the case known as the "para-political" scandal.