In the late 1990s, Miko returned to the United States and landed her first major film role in "Coyote Ugly" in 2000. This was followed with a lead role in the 2001 vampire horror film "The Forsaken", playing a young woman infected by a vampiric virus. In 2005, Miko appeared in a multi-episode story arc on the HBO series "Deadwood"; the same year, she appeared in the music video for "Mr. Brightside" by The Killers (she would again collaborate with the band for the video of their 2012 single "Miss Atomic Bomb", breaking her foot during filming). In 2006, she had a lead role in "Save the Last Dance 2", replacing Julia Stiles from the original film.