On 1 October 2012, President Juan Manuel Santos appointed De La Calle as the government's chief negotiator with the FARC in the Colombian peace process which was hosted in Havana, Cuba. As a result of these peace talks, a final agreement was concluded in September 2016. The agreement was put to a vote in a special referendum in October 2016, during this period the polls were very tight and the campaign became very divisive between the Yes and No campaigns. After a low turnout, the Yes campaign lost with 50.2% voting No and 49.8% voting in favour of the peace accords. After government meetings with the opposition, and Government and FARC representatives, a new agreement based on the original version but with adjustments was signed. The Senate and House of Representatives soon approved the new agreement with substantial majorities. Currently De La Calle continues in his position, now charged with facilitating the implementation of the agreements.