He was a pious, peace-loving monk with no ambition save for the Church, the crusades and the extirpation of heresy. He steered a middle course between the factions at Rome, and sought a settlement of the Sicilian question. In May 1289 he crowned King Charles II of Naples and Sicily after the latter had expressly recognized papal suzerainty, and in February 1291 concluded a treaty with Alfonso III of Aragon and Philip IV of France looking toward the expulsion of James II of Aragon from Sicily. The loss of Acre in 1291 stirred the pope to renewed enthusiasm for a crusade. He sent missionaries, among them the celebrated Franciscan missionary, John of Monte Corvino, to labour among the Bulgarians, Ethiopians, Tatars and Chinese.
He issued an important constitution on July 18, 1289, which granted to the cardinals one-half of all income accruing to the Roman see and a share in the financial management, and thereby paved the way for that independence of the college of cardinals which, in the following century, was to be of detriment to the papacy.
Nicholas died in the palace which he had built beside Basilica di Santa Maria Maggiore.