The Vatican Library thereby possesses the collection established by Federico between the 1460s and 1482 and its subsequent additions, for the most part acquired by the last lord of the Duchy of Urbino, Francesco Maria II Della Rovere (1549-1631). The collection was not subject to many losses or distributions before its transfer to Rome (see Bindings). Instead, after the arrival to the Vatican, other manuscripts unrelated to the original collection were also joined to the Urbino manuscripts, particularly to the Latin ones, since it was considered “open” for the whole of the 18th century.

In the library of the popes, the collection of the dukes of Urbino was divided into different sections according to alphabetical criteria: Urbinati latini (today 1,779 shelfmarks), Urbinati greci (today 165 shelfmarks), Urbinati ebraici (today 59 shelfmarks); six Arabic manuscripts were added to the open Arabic collection (today’s Vat. ar. 155, 212, 216, 221, 228, 229). The significant presence of these last two languages ​​is rare in the libraries of the lords of the time, which were usually bilingual. Nevertheless, the Latin section is certainly the largest; it also includes translations from the Greek and texts in the Italian vernacular, which had by then gained the status of a learned language.

The presence of several ancient inventories that have been transmitted allows us to follow the events from the 15th-century collection up until the Vatican reorganization. The oldest of these, the so-called Indice vecchio, datable to the eighties of the 15th century, allows to have a good picture of the library left by Federico at his death.