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The House of Pepoli is a prominent aristocratic and banking family in Bologna, Italy.

The family reached its apogee in the first half of the 14th century, when they were lords of Bologna, who took power in the chaotic commune riven by the struggles between Guelfs and Ghibellines. Their seat in the city was Palazzo Pepoli Vecchio, constructed by Taddeo Pepoli. The Pepoli maintained dynastic alliances through well-considered marriages: Obizzo III d'Este, Marquis of Ferrara, married Jacopa Pepoli in 1317 and the condottiero Roberto Alidosi, papal vicar and lord of Imola, was given Giacoma Pepoli.

After the happy years of the rule of Taddeo Pepoli (1337—1347), Bologna fell to the Visconti of Milan; though Cardinal Gil de Albornoz forcibly returned the city to the papal orbit in 1360, the Pepoli never regained their former civic power.

The family remained prominent landowners. Guido Pepoli was ordained cardinal by Pope Sixtus V in 1589. The imposing Palazzo Pepoli Campogrande was commissioned in 1653 by the newly minted Senator Odoardo Pepoli; the architects were Giovanni Battista Alberoni and Giuseppe Antonio Torri. Today it houses the Baroque works once in the Pinacoteca Nazionale di Bologna.

A later member of the family, conte Carlo Pepoli, wrote Vincenzo Bellini's libretto for I Puritani and provided the lyrics for Rossini's song "La Danza". To him Giacomo Leopardi dedicated one of his canti.

Napoleone Gioacchino Pepoli was senator of the Kingdom of Italy and Mayor of Bologna, he was also envoy of the Kingdom of Italy in Russia. Moreover he was nephew of Napoleon because its mother was Letizia Murat the daughter of Gioacchino Murat.

The commune of Castiglione dei Pepoli in the Italian Province of Bologna still bears the family's name.