Del Potro started his clay-court campaign of 2012 in the Davis Cup Quarterfinals against Croatia. He won his first rubber against Ivo Karlović and then demolished Marin Čilić in the reverse singles. He continued his clay-court season at the Estoril Open, where he was the defending champion and the top seed. He did not drop a set en route to the finals, where he beat Frenchman Richard Gasquet in straight sets in the final to collect his 11th ATP World Tour title. He next competed in the Madrid Masters as the twelfth seed and defeated Florian Mayer, Mikhail Youzhny, Marin Čilić, Alexandr Dolgopolov, but lost to Tomáš Berdych in the semifinals.