Building work began in 1538, at the request and expense of the people and with the consent of Archbishop Sipontino, Cardinal Giovanni Maria of Monte San Sabino, and Pope Julius III.
The land, which included a cottage and a well, was a donation from Orazio Antonio Landi. The friars came into possession of the land in 1540 and bore witness to God by leading holy lives and receiving divine assistance in return.
Camillo De Lellis was staying there on 1 February 1575 when he decided to change his life following a long conversation with Padre Angelo, the monastery's Father Superior.
1811: the monastery was closed for the first time.
1818: it was reopened.
early 1867: the monastery was closed again.
20th October 1867: ownership of the monastery, church, land, as well as furniture and furnishings was passed over to the local council of San Giovanni Rotondo under the provisions of article 20 of the suppression law of 7 July 1866. The monastery was used as a shelter for the homeless until 1908.
1904: the Provincial, Padre Pio from Benevento, repeatedly tried to persuade the local authorities to return the monastery.
1909: the monastery was returned to Padre Benedetto from San Marco in Lamis and the friars moved into it at the start of September.
28 July 1916: the date when Padre Pio arrived at the monastery. From this time on, the history of the monastery was to be closely associated with the life of the Blessed Father.