After attending Arhus Theatre School, he made his film debut in the movie Pusher. He has starred in popular Danish movies such as Flickering Lights (Danish: Blinkende Lygter), The Green Butchers (Danish: De Gronne Slagtere), his film debut Pusher, and Pusher II. Arguably, Mikkelsen's most famous role was as a cop in the Danish television series Unit One (Danish: Rejseholdet). He also starred in the Jerry Bruckheimer production of King Arthur in which he portrayed Tristan. He also played the villain Le Chiffre in the 21st James Bond film Casino Royale.

Filmography

• Cafe Hector (1996) as Anders
• The Glass House Prisoner(1996) as Max
• Pusher(1996) as Tonny
• Wildside(1998) as Jimmy
• Angel of the Night (1998) as Ronnie
• Tom Merritt(1999) as Tom Merritt
• Bleeder (1999) as Lenny
• Flickering Lights(2000) as Arne
• Monas verden(2001) as Casper
• Shake It All About(2001) as Jacob
• I Am Dina(2002) as Niels
• Open Hearts (Danish: Elsker dig for evigt), (2002) as Niels
• Wilbur Wants to Kill Himself(2002) as Dr. Horst
• Now(2003) as Jakob (young)
• The Boy Below(2003) as dad
• The Green Butchers(2003) as Svend
• Torremolinos 73(2003) as Magnus
• King Arthur(2004) as Tristan
• Pusher II(2004) as Tonny
• Adam's Apples (2005) as Ivan
• After the Wedding(2006) as Jacob
• Prague (2006) as Christoffer
• Exit (2006) as Thomas Skepphult
• Casino Royale(2006) as Le Chiffre
• Flame & Citron(2008) as Citronen (Jorgen Haagen Schmith)
• Quantum of Solace (2008) as Le Chiffre
• Valhalla Rising(2009) as One-Eye

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