[5][6] Pletikosa began his professional career with Hajduk Split in Croatia, transferred to Shakhtar Donetsk in Ukraine, then joined Spartak Moscow in 2007.

He is the fourth-most capped player in the history of the Croatia national team after Luka Modrić, Darijo Srna and Ivan Perišić, having made 114 appearances.

Pletikosa returned to Shakhtar the following season, but found himself second choice to Jan Laštůvka, prompting the goalkeeper to seek a move.

On 7 March, the Russian football federation's transfer deadline day, Pletikosa signed a three-year, €3 million contract to join Spartak Moscow.

But insecurity over the handling of high balls took a heavy toll at the 2000 UEFA European Under-21 Championship in Slovakia, where Croatia finished last in their group.

Under former Croatia head coach Mirko Jozić, he became his country's first-choice goalkeeper, playing all three matches at the 2002 FIFA World Cup finals.

On 16 June 2008, during the match between Austria and Germany, BBC pundit Alan Hansen stated his belief that Pletikosa had been "the best goalkeeper in the tournament" up to that point, ahead of more well-known contemporaries such as Petr Čech, Gianluigi Buffon and Iker Casillas, although his colleague Alan Shearer said Edwin van der Sar had been equally impressive.

On 6 February 2013, Pletikosa played his 100th international match for Croatia, keeping a clean sheet in a 4–0 defeat of South Korea.

[14] Pletikosa is a practising Roman Catholic who was known to wear a T-shirt with a picture of the Virgin Mary under his uniform for good luck when he played.