The sacristy of the Cathedral is rectangular and vaulted with a barrel ceiling, decorated with lateral and angular ribbed vaults featuring garlands, cornucopias, and angels holding a model of the Holy House of the Madonna. At the center of the vault, within a rectangular panel, there is a painting of the Madonna with Child above the Bridge. All the decorations were commissioned by Archbishop Francesco Maria de Luca (Bishop of Lanciano from 1818 to 1834) and were paid for at his own expense.

The sacristy cabinets were built by the Lanciano master carpenter Giacinto Marciani in 1734 and restored in 1996. After the restoration of the decorations and cabinets in the 1990s, the sacristy was equipped with a large central counter made of walnut wood to facilitate the storage and convenient use of linens and liturgical vestments.

The sacristy can be accessed through an entrance located behind the altar or by crossing the corridor-gallery designed by Filippo Sargiacomo, which can be reached via a side opening in the Chapel of the Sacrament.