And 20,000 Argentine fans will cross the Andes hoping that the jinx is ended at the Copa America, starting in Chile on Thursday.
Barcelona's 3-1 victory over Juventus on Saturday provided Messi's fourth Champions League crown in 10 years. He also has seven Spanish titles and two World Club Cups and has been world player of the year four times.
But Argentina's defeat to Germany in the World Cup last year extended a national title drought lasting back to the 1993 Copa America.
But while he was declared player of the World Cup, the Little Genius's speed and jinking runs never seem the same on the international stage as they do when he pulls on a Barcelona shirt.
Messi scored 43 goals in 38 Spanish championship matches this season -- behind eternal rival Cristiano Ronaldo on 48 -- and has the most goals in La Liga history with 286 and also a record 77 in the Champions League. But the rate falls for Argentina, with 45 goals in 97 appearances.
"It's great to play with the national team, to wear the shirt and to be captain," Messi said recently. "But getting a title would be the ultimate for me."
In 2007, Messi was part of the Argentine team that lost the Copa America final 3-0 to Brazil. In 2011, they lost to Uruguay in the quarter-finals on penalties when playing in his home province of Santa Fe.
Argentina start this tournament against Paraguay on Saturday and also play Uruguay and Jamaica in Group B.
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