Melzer lost in the first round of the Australian Open at the start of the season, but then reached the semifinals in Zagreb, losing to defending/eventual champion Marin Čilić. After a quarterfinal appearance in Rotterdam, where he lost to Nikolay Davydenko, Melzer reached the semifinals in Dubai, where he lost to Mikhail Youzhny. Later in the year, Melzer reached the quarterfinals of the ATP Masters 1000 in Madrid, losing to Nicolás Almagro. Melzer followed this up with his best result in a Grand Slam to date by reaching the semifinals of the French Open. He beat Dudi Sela and Nicolas Mahut before he caused a significant upset by defeating ninth seed David Ferrer in straight sets, followed by a four-set win over Teymuraz Gabashvili (who had beaten Andy Roddick in the previous round), and by a five set triumph over Novak Djokovic, coming back from a two-set deficit for the first time in his career. He was eventually defeated by four-time champion Rafael Nadal in straight sets.