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The series revolves around Piper Chapman (Taylor Schilling), a woman in her 30s living in New York City who is sentenced to 15 months in Litchfield Penitentiary, a minimum-security women's federal prison (initially operated by the "Federal Department of Corrections", a fictional version of the Federal Bureau of Prisons, and later acquired by MCC, a private prison company) in upstate New York. Piper had been convicted of transporting a suitcase full of drug money for her girlfriend Alex Vause (Laura Prepon), an international drug smuggler. The offense had occurred 10 years prior to the start of the series and in that time Piper had moved on to a quiet, law-abiding life among New York's upper middle class. Her sudden and unexpected indictment severely disrupts her relationships with her fiancé, family and friends.
In prison, Piper is reunited with Alex (who named Piper in her trial, resulting in Piper's arrest) and they re-examine their relationship. Simultaneously, Piper must learn how to survive in prison, and how to overcome its numerous, inherent struggles. Episodes often feature flashbacks of significant events from various inmates' and prison guards' pasts. These flashbacks typically explain how the inmate came to be in prison, or otherwise further develop the character's backstory.
The show also pays close attention to how instances of corruption, drug smuggling, funding cuts, overcrowding and guard brutality adversely impact not only the prisoners' health and well-being, but also the prison's basic ability to fulfil its fundamental responsibilities and ethical obligations as a federal corrections institution. One of the show's key conflicts involves the prison's Director of Human Activities, Joe Caputo, whose efforts and aims as a warden constantly conflict with the business interests of MCC, which acquired the facility when it was about to be shut down.



Piper Chapman è una donna proveniente dal Connecticut, residente a New York, che viene condannata a scontare quindici mesi al Litchfield, un carcere federale femminile gestito dal Dipartimento Federale di Correzione, per aver trasportato una valigia piena di soldi di provenienza illecita per Alex Vause, una trafficante di droga internazionale e un tempo sua amante. Tale infrazione è accaduta dieci anni prima dell'ingresso della Chapman in carcere e negli anni intercorsi tra l'inizio del processo a suo carico e la condanna, la donna è riuscita a costruirsi un'agiata vita, rispettosa della legge, con il suo nuovo fidanzato Larry Bloom, nell'alta borghesia newyorkese.
Dietro le sbarre, Piper rincontra Alex (che avrebbe fatto il nome della Chapman durante il suo processo, causandone l'arresto), alla quale, nonostante un iniziale astio, si riavvicina. Oltre a loro, in carcere convivono tante altre donne, le cui storie vengono raccontate tramite l'utilizzo di flashback.