The manuscripts in Trinity College Dublin are predominantly from the library of Archbishop James Ussher (1581-1656). A well-known bibliophile of the sixteenth century, he was also primate of All Ireland and fellow and professor of Trinity College. Following some movement of the collection, it was eventually returned to Trinity College after the Restoration, at the behest of Charles II.

It is a significant collection, both in national and international terms, with over 600 manuscripts, 79 of which contain Middle English prose. Among the manuscripts in the collection are several Wycliffite Bibles, and collections of sermons and tracts, some of them unique copies. The collection also contains writings by Richard Rolle, Walter Hilton and William Flete, and copies of Thomas à Kempis's Imitation of Christ, as well as the Pore Caitif and The Cloud of Unknowing, both of which are anonymous. There are several copies of the Brut chronicle, two of which (MSS 489 and 505) are illuminated, translations of Giraldus Cambrensis's Expugnacio Hibernica, and a copy of Robert Bale's Chronicle of London, 1189-1461. Also of note are the various collections of recipes - medical, culinary and alchemical. Dictionary-style items demonstrate the trilingual nature of the Medieval period, with single words being offered in English alongside Anglo-Norman and/or Latin words, or as marginal glosses. Fifteenth-century instructions for the coronation of a King or Queen, hidden among some later material, as well as other unidentified heraldic pieces, suggest that some of the manuscripts may be associated with the office of the Ulster King of Arms.

The current handlist covers 79 manuscripts, and indexes more than 539 separate items, offering a significant contribution to the understanding of the cultural world of the Medieval period.