Grand Master Jean de la Cassière commissioned the church for the Order of St John after the Great Siege of 1565, and the Maltese architect Girolamo Cassar designed it. The infobox gives 1572 for groundbreaking, 1577 for completion and February 20, 1578 for consecration, while the lead says it was built from 1573 to 1578.
The exterior is Mannerist, plain and fortress-like, flanked by two bell towers. The interior is high Baroque, largely decorated by Mattia Preti in the 1660s with carved limestone walls and ceiling paintings of John the Baptist. The church is 213 feet (65 m) long and 130 feet (40 m) wide. The nave floor is made of marble tombstones covering about 400 knights and officers.
Caravaggio's The Beheading of Saint John the Baptist of 1608, his largest canvas and the only one he signed, hangs in the oratory. Visitors pay an entrance fee, except those attending Mass.

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