"From the outset, the Russian Federation was not an exclusive ally of Syria or President Assad," Dmitry Medvedev told CNN at the World Economic Forum's annual meeting in Davos, Switzerland.
"We used to have good relations with him and his father [Hafez Assad], but he had much closer allies among the Europeans," Medvedev said.
He repeated Russia's longtime insistence outside powers shouldn't pick Syria's leaders.
Russia "never said that our goal was to preserve the current political regime, or making sure that President Assad stays in power," he added. "That decision has to be made by the Syrian people."
Medvedev said he personally appealed to Assad to open up his regime to reform and said Assad's refusal have serious talks with part of the moderate opposition was an "important, if not fatal" mistake.
"The chances for him surviving are slipping away as days and weeks go by," Medvedev told CNN. "But once again, this should not be up to us. It should be up to the Syrian people."
Medvedev placed equal blame for the escalation of the 2-year-old civil war on "the leadership of the country and the irreconcilable opposition."
He warned that if Assad's rule is "swept away" by the revolt, the resulting conflict among its successors could last "for decades."
Asked about concerns jihadists in Syria could spread into southern Russia, where Islamic militant groups have been battling Moscow for more than a decade, Medvedev said such a prospect should alarm the West as well.
"They can travel to Europe. They tried to. And in the U.S.," Medvedev said. "So it is alarming for all of us. It does not mean, though, that we should bring to power radical opposition leaders. It should be a difficult process, led by civil society."
The Syrian conflict led to at least 106 deaths Sunday, including five women, 11 children and three people who were tortured to death, the opposition Local Coordination Committees reported.
The United Nations says more than 60,000 people have died in the conflict that began in March 2011.