Three years after the first film, first summer after college, the girls are separate until the Pants reunite them. Bridget (Blake Lively) visits her grandmother Greta (Blythe Danner) in Alabama, to ask about her mother's suicidal depression. Lena (Alexis Bledel) finds Kostas (Michael Rady) married in Greece. Tibby (Amber Tamblyn), fearing pregnancy, alienates Carmen. Carmen (America Ferrara) auditions for Perdita in a Vermont acting workshop. When Lena's sister Effie (Lucy Hale) steals and loses the Pants in Greece, the Sisterhood follow. Despite not finding the Pants, they do convince Lena to take back Kostas.

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