Biden, the most senior American official to visit Cyprus since his predecessor Lyndon Johnson in 1962, voiced strong support for a new round of talks to reunify the island, which was divided along ethnic lines in 1974 when Turkey invaded after a coup by supporters of union with Greece.
"This island can, and should be the bedrock of stability and opportunity for Europe and for the eastern Mediterranean," Biden told reporters after touching down at the country's main airport.
"I've travelled today because I believe that this time, can be different," Biden said. "Whether it will, depends on the people of this island."
He quashed speculation that he would either "impose or present" a peace deal during his visit, saying that an accord bringing "incredibly greater prosperity" and greater security can only come from Cypriots themselves.
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He also eased Greek Cypriot concerns that his visit with Turkish Cypriot leader Dervis Eroglu in the breakaway north of the island would impart any official recognition, saying his contacts wouldn't change long-standing US policy.
A Cyprus peace deal would have regional repercussions as it could help mend strained relations between key US regional allies Turkey and Israel. Those countries fell out after Israeli commandos stormed a Turkish ship trying to break the Israeli blockade of the Gaza Strip in May 2010.
A reunified Cyprus could also act as a conduit to transport Cypriot and Israeli gas to Europe through Turkey via a pipeline, helping to reduce the continent's energy dependence on Russia, which has threatened to cut deliveries amid the Ukrainian crisis.