[2] Maffei was named a cardinal by Pope Paul on 11 September 1606, and assigned the deaconry of San Giorgio in velabro on 9 October.

On 7 February 1607, he was promoted cardinal-priest, and assigned the titular church of Ss.

[1][5] Having been archbishop of Chieti for less than a year, he found himself in trouble with Pope Paul V, due to accusations which included violation of his vow of chastity with a woman of the diocese.

[6] He was buried in the family tomb in the church of Santa Maria sopra Minerva in Rome.

[7] Francesco Maria Guazzo (Guaccius) dedicated the first edition (1608) of his book, Compendium maleficarum, to Cardinal Orazio Maffei, the Protector of the Ambrosian Order, of which Guazzo was a member.