The dome is 16.10 metres (54.3 ft) in diameter and 80 metres high, making it the third highest dome in Rome, exceeded only by that of St. Peter's Basilica in the Vatican and the newer dome of the Church of Saints Peter and Paul in the EUR. It was designed by Carlo Maderno.

The fresco decoration of the dome was one of the largest commissions of its day, by Cardinal Alessandro Peretti di Montalto. Giovanni Lanfranco's dome fresco is the Glories of Paradise, painted 1622-1625. The paintings of the Four Evangelists in the pendentives are by Domenichino.