Following the hand-over of the Castle by the military authorities to the City of Milan in 1893, an extensive and protracted renovation of the fort supervised by the architect Luca Beltrami began. Between 1907 and 1908, thanks to the generous donation of the Mangili family, the architect also worked on the Spanish Hospital.

During the works, the top floor, which was built between the 18th and 19th century, was demolished, while the internal areas of the building remained untouched.  The exterior facade was decorated with elaborate red monochrome motifs taken from the decorations of the ceiling of the early 16th century Milanese Church of Santa Maria della Fontana.

Following the decision to transform the old hospital into the new Museo della Pieta Rondanini, significant restorations were started in July 2013 to strengthen the structure, rendering it earthquake and vibration resistant so as to protect the masterpiece and bring to light the original decorative paintings. The Museo della Pietà was inaugurated on 2 May 2015.