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After graduating from Brown with a degree in English, she visited India with her boyfriend Alex Fineman and came down with amoebic dysentery. Recovered, Andrea leaves her home in Avon, Connecticut for New York City. There she moves in with her longtime friend Lily, now doing graduate studies in Russian at Columbia, and looks for a job. A longtime reader of The New Yorker, she blankets the magazine publishing industry with her résumé, hoping to land enough experience somewhere and eventually get a job at the prestigious weekly. Still not over her dysentery, she gets a surprise interview at the Elias-Clark group. Afterwards she is hired as Miranda's junior assistant. While she knows little of her, she is told repeatedly that "a million girls would die for your job." Even happened Andrea Sachs was stuck in midtown Manhattan traffic, trying to remember how to use a manual transmission. She has picked up her boss's Porsche roadster, Runway magazine editor Miranda Priestly, from a shop and must get it to Miranda's apartment in time for Miranda's family to go to the Hamptons for the weekend. While she is attempting to do this, Miranda calls on her cell phone and excoriates her for not doing her job properly. She also tells her to pick up her pet French bulldog from the veterinarian's office. Trying to comply, Andrea ruins some of the expensive designer clothing she is wearing. She wishes Miranda would die. But if that did happen, she reminds herself, she'd lose the pleasure of killing Miranda herself. Andrea is told that if she manages to stick it out working for Miranda for a year, she can have her select pick of jobs within the magazine industry, so she valiantly struggles onward. Even in the present, the perks aren't bad — between Runway's notorious "closet" of designer clothes ostensibly "on loan" for photo shoots but rarely returned and often "borrowed" by the staff and the general obsequiousness she encounters as Miranda Priestly's personal assistant, she is able to acquire enough free designer clothing to fit in better with the rest of the fashionable Runway staff. Eventually, she develops an appreciation for it and stops incurring Miranda's displeasure. She gets a Bang and Olufsen phone for free when Miranda doesn't want it, and learns that Elias-Clark's policies regarding expense accounts are rather lax, to the benefit of herself and her friends. She also goes to parties with celebrities. At one of them she meets Christian Collinsworth, a Yale graduate who has been identified as the hot (in more ways than one), up-and-coming writer of their generation. They become attracted to each other, complicating her relationship with Alex. Her job, however, begins to affect her health; she starts to lose weight because she can't bring herself to eat. This is due to the fact that she knows that she, after years of being tall and fairly thin, is now the fat, lumpy dwarf. Eventually, she begins to rationalize her not eating by thinking that: "Missing one meal won't hurt, and anyway, $2000 pants don't
look so hot on a fat girl." She realizes that she, in that thought, has begun to embody the Runway attitude. While working for Miranda, she receives a letter from a teenager, telling Miranda that she loves her magazine, spends all her money on trying to look like the models, but still hates herself because "my butt is huge" and "I'm too fat". The teenager begs Miranda to send her a dress to wear to her prom, but ends by telling her that, even if she throws the letter in the trash can, she'll still love her. Andrea begins to doubt the true value of her job, as it is, primarily, encouraging the woman who makes teenagers all over America hate themselves as much as this one. However, she keeps going, thinking that it will all be worthwhile when she gets a job at The New Yorker. The 14-hour days she puts in almost routinely leave her little free time to spend with Alex and with Lily, who increasingly turns to alcohol and picks up dubious men to relieve pressures of graduate school. Her relationship with her family also suffers. Her parents complain she doesn't visit her older sister, who expects her first child. Andrea ignores all this, even to the point of staying at work when Lily is arrested for going 'bottomless' while on a date with her latest dubious conquest. Matters finally come to a head when Emily gets mononucleosis and Andrea must travel to Paris with Miranda. Andrea agrees, although this will mean canceling her trip for Alex's homecoming weekend, which has dire consequences on her relationship with Alex. In Paris, she has a surprise encounter with Christian. Later that night, Miranda finally lets down her guard a little bit and asks Andrea what she's learned, and where she'd like to work afterwards. She promises to place phone calls to people she knows at The New Yorker on Andrea's behalf once her year is up, and tells her she can actually do some small written pieces for Runway. But back at the hotel, she gets two urgent calls from Alex and her parents asking her to call them. She does so and learns that Lily is comatose in the hospital after driving drunk and wrecking a car. Though Andrea is receiving pressure from her family and Alex to return home, she tells Miranda she will honor the commitment. Miranda is greatly pleased, and tells her that her future in magazine publishing is looking bright. At the Paris fashion show for Christian Dior, however, a livid Miranda phones her. After she hangs up, Andrea stares at her phone, trying to think how to accommodate Miranda's impossible demand. Then, Andrea finally realizes that her family and friends are more important than her job, and realizes that she is becoming more and more like Miranda. On the spot, Andrea flips out her cell phone and tells her family that she's coming home. Miranda disapproves, but Andrea tells Miranda publicly "Fuck you, Miranda. Fuck you." She is fired on the spot, but returns home to reconnect with her friends and family. Her romantic relationship with Alex is beyond repair, but they remain friends. Lily recovers and fares well in court for her DUI charge, receiving only community service.
The fallout from her standup to Miranda made her a minor celebrity when the incident made ‘Page Six’. Afraid she had been blacklisted for good from publishing, she stays in Connecticut for a while and works on short fiction. Seventeen buys one of her stories, and Andrea begins a friendly and professional relationship with Loretta, one of the editors of the teen magazine, who also happened to work for Runway prior to her tenure there. She returns to New York and gives herself a comfortable financial cushion by selling all the designer clothing she took to Paris with her to consignment shops. She saves a pair of Dolce and Gabbana denim jeans for herself, gave a quilted Prada purse to her mother, and a Diane von Fürstenberg wrap dress to the teenager who wrote to Miranda. At the end, she is returning to the building to discuss a position at company's magazines. She arrives in the lobby to hear her friend, Eduardo the security guard, singing "American Pie", the goodbye song she never got to sing. She looks round, and realizes that it is, in fact, Miranda's new junior assistant, who is having to sing in order for Eduardo to let her through, while loaded with Miranda's coffee, shopping bags, newspapers, and her beaded clutch, and she remembers that that used to be her. Eduardo winks.