Nobility. Diego was the third-born son of Innico III d'Avalos (son of Cesare d'Avalos and Lucrezia del Tufo) and Isabella d'Avalos (eldest daughter of Lavinia Feltria Della Rovere and Alfonso Felice d'Avalos, as well as universal heir of this last). After having purchased the city of Isernia from the Duke of Montenero Carlo Greco in 1644, for the sum of 21,000 ducats, he requested and obtained the title of "Prince of Isernia" (created for him ex novo). The Marquis Diego d'Avalos, with the consent of the Royal Court (dated 21 August 1645), sold the fiefdom of Padula to the Certosa di San Lorenzo for 60,000 ducats. The Masaniello revolt exploded in the summer of 1647, Diego and his elder brother Ferdinando Francesco d'Avalos (1601-1665) joined forces to counter the spread of the revolt in their fiefs. Following the deposition of Masaniello and the establishment of the Neapolitan Republic under the guidance of Duke Henry II of Guise and the gunsmith Gennaro Annese, the two brothers went with their armed men (in total 190 knights and 220 infantrymen) to Aversa, where the loyalist forces were concentrating. They participated in the clashes of Nola, Secondigliano, Caivano, until the definitive liquidation of the Neapolitan Republic in 1648. Following the death of his elder brother in 1665, Diego d'Avalos succeeded him in the ownership of the marquisate of Vasto, in 1666 he was confirmed by the Neapolitan government as feudal lord of Ischia as well as captain of the relative castle, in 1687 he also obtained the title of Marquis of Pescara. According to other sources, the death of Ferdinando Francesco d'Avalos would have occurred in 1648 and Diego took over the ownership of the marquisate of Vasto and the marquisate of Pescara in that year. On 12 December 1682 he bought the land of Montenero and the hamlet of Montelateglia. In 1684 Diego d'Avalos was accused by Viceroy Gaspar Méndez de Haro of conducting smuggling practices in his lands and of promoting banditry. Prince Diego d'Avalos d'Aquino d'Aragona distinguished himself for his huge contributions aimed at embellishing and increasing the prestige of Vasto, capital of his feudal domains. He favored the opening in the Abruzzo town of one of the two colleges of regular clerics of the Mother of God which, according to the testament left by Princess Felice Maria Orsini, should have been established in Italy (the other was established in Naples in 1647 at the church of Santa Maria in Portico). In 1689 the clerics took possession of their seat, the church of the Carmine. He also had the chapel of the Holy Thorn built in the church of S. Maria, in order to house this important relic donated by Pope Pius IV to Francesco Ferdinando d'Avalos on the occasion of the Council of Trent (in which the latter had held the functions of ambassador of the king of Spain Philip II of Habsburg) and later ceded by his son Alfonso Felice d'Avalos to the church of Vasto. Prince Diego d'Avalos d'Aquino d'Aragona employed the scholar and historian Francesco Agricoletti as secretary. Another character who was in the service of Diego d'Avalos as his secretary was the Apulian Tommaso Palma, known mainly for having drawn up and printed (in 1690) one of the first treatises on the local history of Vasto, entitled Historical Compendium of the ancient land of the Vasto. Prince Diego d'Avalos d'Aquino d'Aragona died on March 4, 1697, being buried next to his wife (who died in 1692) in the church of the Capuchin convent (also known as the church of Sant'Anna) in Vasto.He was succeeded by his third son Cesare Michelangelo d'Avalos.