He painted in a style that rejected the Mannerism popular in the Naples of his time and evident in the works of Francesco Curia.
He may have been one of the collaborators of Pino on the decoration of the church of S Giovanni Fiorentini in Naples.
[2] He traveled extensively, including to Bologna, Florence, Rome, and Venice in his study of the great masters.
He painted extensively in Naples, including an Assumption and Coronation of the Virgin for Santa Donna Regina Nuova.
Legend has it that during the sack of Naples in 1647 by insurgents under Masaniello two houses in which Santafede had painted frescos were spared out of respect for the artist.