Isner next played at the 2011 Australian Open He entered the tournament seeded 20th and received a tough draw, including Radek Štěpánek, Marin Čilić, and Rafael Nadal. Isner came up against French world no. 69 Florent Serra, whom he easily defeated. Isner then faced Štěpánek in the second round where he would progress into the third round, rallying to ultimately win the match after losing the first set. He next faced fellow top 20 player Marin Čilić. The match went to five sets, with Čilić emerging as the eventual winner.