Medvedev, who was sworn in to succeed Vladimir Putin earlier, took command in the presence of Defence Minister Anatoly Serdyukov at a sombre meeting that contrasted with his glittering inauguration ceremony.
"Comrade commander-in-chief! Allow me to give you control of the strategic forces of the country," said the officer carrying the nuclear briefcase, in images shown on state television.
The nuclear briefcase, a symbol of political power in Russia since the Cold War, is shrouded in secrecy but believed to contain a small computer with activation codes for nuclear missiles.
Russia's first post-Soviet president, Boris Yeltsin, reportedly came close to using the briefcase in January 1995 when a research rocket launched from Norway activated Russia's early warning system.
The briefcase was developed during the Cold War when it became clear that early warning of a nuclear attack would only give Soviet leaders a few minutes to retaliate -- too little time to travel to a central command centre.
Russia is currently estimated to have around 20,000 nuclear weapons.