The Venetian–Genoese Wars were a series of struggles between the Republic of Genoa and the Republic of Venice, at times allied with other powers, for dominance in the Mediterranean Sea between 1256 and 1381. There were four bouts of open warfare, in which the fighting between the two republics took place largely at sea. Even during periods of peace, incidents of piracy and other minor outbreaks of violence between the two trading communities were commonplace. In the first war, in 1256–1270, the Venetians had the better of the fighting, but were unable to prevent the advance of Genoese interests in Byzantium and the Black Sea. The Genoese were overwhelmingly victorious in combat in the second war, 1294–1299. The conflict ended inconclusively, as did the third, 1350–1355, in which Venice fought in conjunction with Aragon and in which the fighting was more evenly balanced. In the fourth war, 1377–1381, Venice itself was threatened with capture by the Genoese and their allies. Although victorious in the fighting, the exhausted Venetians accepted peace terms which amounted to defeat. War of 1256–1270 The first full-scale conflict between Genoa and Venice arose from a dispute over prerogatives in Acre, which led to a Genoese attack on the Venetian quarter. The Venetians were supported by the Pisans and Provencals, the Knights Templar and some of the local nobility, while the Catalans, Valencians, Anconitans, Knights Hospitaller and other local nobles joined the Genoese. A fleet sent from Venice under Lorenzo Tiepolo in 1257 defeated a Genoese fleet off Acre when it arrived in June the next year. In 1261, Venice suffered a major setback with the signing of the Treaty of Nymphaeum between Genoa and the Nicaean emperor Michael VIII Palaiologos, and with Michael's reconquest soon afterwards of the old Byzantine capital of Constantinople from the Latin Empire of Constantinople, effectively a client state of Venice. This permanently destroyed the commercial dominance in the imperial capital and the Black Sea beyond which Venice had enjoyed since the city's capture by the Fourth Crusade in 1204. Throughout the war, the Venetian navy retained the upper hand over the Genoese in naval combat, as the Genoese navy often avoided battle. The major battles that did occur, at Acre in 1258, at Settepozzi in Euboia in 1263 and off Trapani in Sicily in 1266, were clear Venetian victories. However, the concentration of the Venetian fleet left Genoese commerce largely unmolested,