In Samos and Romania
While in Istanbul, he was appointed Prince of Samos (1854 - 1859), where he proved his leadership skills by extirpating local piracy (most of which was aimed at transports supplying the Crimean War). After completing the task, Ghica was awarded the honorary title of Prince of Samos by Sultan Abd-ul-Mejid I in 1856.
In 1859, after the union of Moldavia and Walachia had been effected, Prince Alexandru Ioan Cuza asked Ion Ghica to return. Later (1866), despite being trusted by Prince Cuza, Ghica took active part in the secret grouping that secured Cuza's overthrow. He was the first prime minister under Prince of Romania (afterwards King of Romania) Carol of Hohenzollern.
Ghica is also noted as one of the first major Liberal figures in the Kingdom of Romania, and one of the leaders of the incipient Liberal Party. His group's radicalism, with its boyar leadership that had engineered the defunct Revolution, surfaced as republicanism whenever Carol approached the Conservatives; Ghica joined the anti-dynastic movement of 1870-1871 that had surfaced with the Republic of Ploieşti. The matter of the Liberals' loyalty was ultimately settled 1876, with the exceptionally long Liberal Ministry of Ion Brătianu. In 1881, Ghica was appointed Romanian Minister in London, an office he retained until 1889; he died in Ghergani, Dâmboviţa County.
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