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Starwood Hotels has become the first US hotel company to a agree a deal to invest in properties on the island.
Marriott also confirmed it was in discussions to “develop a hospitality relationship with potential partners” in Cuba.
The Starwood deal came ahead of this week’s historic visit by president Obama, the first by a US president in almost 90 years.
Starwood is to renovate and run three hotels in the Cuban capital of Havana.
A company spokesman said it would be making a “multimillion-dollar investment to bring the hotels up to our standards”.
Starwood becomes the first US company to agree a deal with the Cuban authorities since the revolution of 1959.
Marriott chief executive Arne Sorenson, who is travelling with Obama to Cuba, said: “We are gratified to receive permission from the US government to pursue business opportunities in Cuba.
“While there is still work to do before any agreement is reached, we are actively pursuing relationships in the hospitality sector.
“We have long been convinced that with the right frameworks in place, new economic opportunities, including dramatically expanded travel, abound in Cuba.
“These could deliver real benefits to the Cuban people and also have the effect of bringing both Americans and Cubans closer together.”
The Obama administration has eased some travel restrictions and the president is tipped to reveal more US investment into Cuba during his visit, with airlines and cruise lines keen to tap into the booming tourism market.
The Hotel Inglaterra, which opened in 1875, is one of a trio of hotels Starwood will manage.
Starwood is the target of potentially the biggest takeover of an American company by a Chinese business.
Anbang Insurance, which already owns New York’s Waldorf Astoria, has made a $13 billion bid for Starwood, trumping an offer by Marriott.
Anbang’s founder, chairman and chief executive Wu Xiaohui is married to Zhuo Ran, grand-daughter of Deng Xiaoping, the country’s former leader who is credited with engineering China’s economic reform, the BBC reported.