The Hospital de Santiago, located in the city of Úbeda, is a monument of great architectural value designed by Andrés de Vandelvira in 1562 and completed in 1575, as indicated by the inscription on its main staircase. It is considered one of the most outstanding works of this architect and a reference in the welfare architecture of the Renaissance in Spain. Its construction was ordered by Don Diego de los Cobos, bishop of Jaén, with the purpose of serving as a hospital for the sick poor, as well as a church-pantheon and palace. In 1917 it was declared a national historic architectural monument and currently serves as a cultural center, a venue for exhibitions and congresses, as well as housing a library. Its patrimonial importance has earned it recognition as a World Heritage Site, forming part of the Renaissance monumental complex of Úbeda and Baeza.

The building, both sober and imposing, has a large volume design with minimal ornamentation. Its façade is flanked by two towers covered with glazed ceramic, while two other towers frame the central chapel. Due to its structure, it has sometimes been compared to El Escorial in Andalusia. The distribution of the space is organized around a large central courtyard, with double arches, which stands out for its luminosity and balanced proportions. The white marble columns that support it come from Carrara. On either side of the building are two side courtyards, which were left unfinished. The main entrance is formed by a semicircular arch with large voussoirs, following the Castilian style, and above it is a tabernacle with a relief of Santiago Matamoros, patron saint of the hospital.

On the access axis is the chapel, protected by an impressive three-door grille, designed by Vandelvira and forged by Juan Álvarez de Molina. Its structure is innovative because of its H-shaped plan, with two towers displaced towards the center of the church. At the back, the choir loft follows the model of the churches promoted by the Catholic Monarchs.

From one side of the main courtyard rises a monumental cloister staircase, covered by a peculiar suspended vault with Hispano-Islamic influences. Its walls are decorated with frescoes, made shortly after the completion of the building, attributed to Pedro de Raxis and Gabriel Rosales, also responsible for the main altarpiece, destroyed in 1936. Similar paintings, in Mannerist style with Italian-Classical influences, adorn the vaults of the church, the sacristy and the antero-christy, making it one of the few preserved examples of Renaissance mural painting in Spain.