According to Ottoman tradition, when Orhan succeeded his father, he proposed to his brother, Alaeddin, that they should share the emerging empire. The latter refused on the grounds that their father had designated Orhan as sole successor, and that the empire should not be divided.
By 1326, lands around Nicaea had fallen into the hands of Osman I. He had also captured the city of Bursa, establishing a capital dangerously close to the Byzantine capital of Constantinople. In 1328, Orhan, Osman's son, began the siege of Nicaea, which had been in a state of intermittent blockade since 1301. The Ottomans lacked the ability to control access to the town through the lakeside harbour. As a result, the siege dragged on for several years without conclusion. In 1329, Emperor Andronicus III attempted to break the siege. He led a relief force to drive the Ottomans away from both Nicomedia and Nicaea. After some minor successes, however, the force suffered a reverse at Pelekanon and withdrew. When it was clear that no effective Imperial force would be able to restore the frontier and drive off the Ottomans, the city proper fell in 1331.
A twenty-year period of peace followed the acquisition of Karesi. During this time, the Ottoman sovereign was actively occupied in perfecting the civil and military institutions which Orhan's brother had introduced, in securing internal order, in founding and endowing mosques and schools, and in the construction of vast public edifices, many of which still stand. Orhan did not continue with any other conquests in Anatolia except taking over Ankara from the commercial-religious fraternity guild of Ahis.
The Black Death was destructive for the Byzantine state. It arrived in Anatolia in late 1346 and reached Constantinople in 1347. As in Europe, the Black Death eliminated a significant proportion of the population in the capital and other towns and aggravated the already poor economic and agrarian conditions in cities and the countryside. The Black Death devastated Byzantium especially because it occurred after two civil wars over succession, in the 1320s and 1340s, which left the state stripped of cash and vulnerable to Venetian, Genoese, and Ottoman intervention and invasions. From 1346 to 1352, the epidemic ravaged Byzantine cities, depleting their populations and leaving few soldiers to defend them.
Ottomans gained their first permanent stronghold in Europe at Çimpe Castle in 1354. It was granted to the Ottoman Turks by the Byzantine emperor John Kantakouzenos around 1352 for their use during his war against his erstwhile charge and co-emperor John Palaiologos.
Orhan died in 1362, in Bursa, at the age of eighty, after a reign of thirty-six years. He is buried in the türbe (tomb) with his wife and children, called Gümüşlü Kumbet in Bursa. Orhan was the longest living and one of the longest reigning of the future Ottoman Sultans. In his last years he had left most of the powers of state in the hands of his second son Murad and lived a secluded life in Bursa.