Milito made his Argentina debut on 31 January 2003 against Honduras, where he also scored his first goal. He scored his second and third goals on 16 July 2003 against Uruguay, but appeared only intermittently during the following years and was omitted from the 2006 World Cup squad. He played for Argentina in the 2007 Copa América tournament, gaining playing time after Hernán Crespo's injury in a Group Stage match against Colombia, where he scored a goal; Argentina progressed to the final, where they were defeated 3–0 by Brazil.