- Chiwetel Ejiofor as Peter
- Colin Firth as Jamie
- Gregor Fisher as Joe
- Hugh Grant as David, the Prime Minister
- Sienna Guillory as Jamie's girlfriend
- Keira Knightley as Juliet
- Andrew Lincoln as Mark
- Laura Linney as Sarah
- Martine McCutcheon as Natalie
- Lúcia Moniz as Aurélia
- Liam Neeson as Daniel
- Bill Nighy as Billy Mack
- Alan Rickman as Harry
- Thomas Sangster as Sam
- Rodrigo Santoro as Karl
- Emma Thompson as Karen
- Joanna Bacon as Natalie's Mum
- Brian Bovell as Radio Watford DJ
- Kris Marshall as Colin
- Abdul Salis as Tony
- Heike Makatsch as Mia
- Martin Freeman as John
- Joanna Page as Judy
- Olivia Olson as Joanna
- Billy Bob Thornton as the U.S. President
- Rowan Atkinson as Rufus
- Claudia Schiffer as Carol
- Nina Sosanya as Annie
- Ivana Miličević as Stacey
- Margery Mason as Harris Street old lady
- Gillian Barge as cabinet minister
- Ivana Miličević as Stacey - American dreamgirl
- John Sharian as Wisconsin taxi driver
- Wyllie Longmore as Jeremy
- Dan Fredenburgh as Jamie's bad brother
- Lynden David Hall as the wedding singer
- Sheila Allen (English actress) as Jamie's Mum
- Junior Simpson as Wedding DJ
- Jo Whiley as Radio DJ
- January Jones as Jeannie - American angel
- Elisha Cuthbert as Carol-Anne - American goddess
- Laura Rees as record company executive
- Wes Butters as Radio 1 Chart Show DJ
- Shannon Elizabeth as Harriet
- Lulu Popplewell as Daisy
- Marcus Brigstocke as Mikey
- Julia Davis as Nancy
- Ruby Turner as Jean
- Adam Godley as Mr Trench
- Élisabeth Margoni as Eleonore
- Edward Hardwicke as Sam's grandfather
- Caroline John as Sam's grandmother
- Meg Wynn Owen as Mary, the PM's secretary
- Ruby Turner as Mrs Jean Anderson
- Adam Godley as Mr Trench
- Nancy Sorrell as Greta
- Shannon Elizabeth as Harriet - the sexy one
- Denise Richards as Carla - the real friendly one
- Richard Curtis as trombone player (uncredited)
- Rebecca Frayn as Joanna, Daniel's wife (uncredited)
- Jeanne Moreau as taxi passenger Marseille Airport (uncredited)
- Anthony McPartlin as TV host Ant (himself)
- Declan Donnelly as TV host Dec (himself)
- Michael Parkinson as TV host Parkinson (himself)
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