Isla made his professional debut on 19 December 2007 versus Palermo in the Coppa Italia. On 8 March 2008, Isla played his first game as a starter in Serie A also against Palermo, a game which ended in a 1–1 draw. After the departure of Simone Pepe, Isla often played as a right wing-back in a 3–5–2 formation during Udinese's 2010–11 Serie A campaign, due to a long-term injury to Dušan Basta. In that season, he was instrumental in helping Udinese finish fourth, thus gaining qualification to the 2011–12 UEFA Champions League play-off round.