He made a name for himself with Porto in Portugal, where he spent four seasons and won ten major titles, including three Primeira Liga championships and the 2011 Europa League.

Guarín made his debut for the French side scoring twice in a friendly against RCD Espanyol, and gradually fought his way into the starting lineup as the season closed.

[5] During his spell he was used mainly as a substitute, but managed to appear regularly;[6] arguably, his most important goal came on 16 May 2010 as the team renewed their Taça de Portugal title, defeating G.D. Chaves 2–1.

He was, however, a very important midfield element for the eventual national champions, playing more than 40 official games and scoring ten goals,[8] including five in the Europa League campaign,[9][10][11][12][13] which also ended in conquest.

[14] Guarín joined Inter Milan on 31 January 2012 for €1.5 million, on loan, with the player replacing Paris Saint-Germain FC-bound Thiago Motta.

[21] In the January 2014 transfer window, he was supposed to move to Juventus FC in exchange for Mirko Vučinić, but the deal ultimately fell through after the clubs could not reach an agreement.

[28] On 7 December 2014, in his 100th appearance for Inter, Guarín assisted Mauro Icardi in the 44th minute of an eventual 1–2 home defeat to Udinese Calcio.

[38] He played his first game in the tournament on 24 June after the national team had already won its first two group matches, featuring the full 90 minutes in a 4–1 win against Japan which was also his 49th cap;[39] he earned his 50th four days later, coming on as a late substitute to help oust Uruguay 2–0 in the round of 16.

[41] A versatile player, Guarín was a strong, fast and creative attacking midfielder, who could also play in the centre, in a holding role or on the right flank.