At the beginning of the seventeenth century, under Pope Paul V, the archival portion was separated from the rest of the Library; it became the Vatican Secret Archives. The Library’s collections were organized in a way which has remained fundamentally unaltered to the present day. The seventeenth century also saw the addition to the Library of entire private collections, which in many cases became “closed” collections of manuscripts and printed books within the Vatican Library and have remained distinct from the other, open collections. In 1632, the Palatine Library of Heidelberg, which had fallen into the hands of the Duke of Bavaria Maximillian I as war spoils, was donated by him to Gregory XV in gratitude for the help he had received from the Holy See during the Thirty Years’ War; in 1657, the Library acquired the manuscripts of the Dukes of Urbino; in 1689 it purchased the manuscripts previously collected by Queen Christina of Sweden. Other large accessions were the Capponi collection in 1746 and the Ottoboni collection in 1748.

In the eighteenth century the idea of publishing a complete catalogue of the manuscripts preserved in the Library emerged. Of the grandiose series envisaged by Giuseppe Simonio Assemani and by his nephew Stefano Evodio, which was to comprise twenty folio volumes, only the first three volumes and an incomplete fourth one were actually produced. At the end of the century, the Library’s collections were diminished by the war tribute which was imposed on the Holy See by Napoleon; but many of the relevant books and objects were returned in 1815.

Typical of the eighteenth century was the establishment and the steady growth within the Vatican Library of artistic and antiquarian collections. The first of these were in the Numismatic cabinet, augmented in 1738 by the acquisition of the collection of Roman and Greek medallions owned by Cardinal Alessandro Albani, which, at that time, was the largest collection in existence after that of the King of France. The Museum of Sacred Art was founded in 1757 by the merging of three important collections, and was continually enriched by various types of objects from Christian antiquity (ivories, enamels, bronzes, glass, terracottas, textiles, etc.), coming mostly from the Roman Catacombs. In 1767, the Museum was subdivided into two parts, giving rise the Museum of Secular Art. This collection also suffered grave losses due to the events of the end of the century; in particular, a large portion of the numismatic collection was removed and only partially recovered later.