The theft occurred at the Bank of Baroda's Ramapuram Kundarapalli branch here.
Police said the robbers accessed the vault by breaking open the rear door of the bank.
"Forty-eight kg and 308 gm of gold was looted by the robbers, who broke open one of the three lockers with gas- based welding equipment. The theft could have happened late last night or early this morning," Guruparapalli Police Inspector J Rajendran told PTI.
Top police officials visited the spot. Ten separate teams have been formed to nab the culprits.
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Investigators are also scanning the CCTV camera footage of the bank to zero-in on them.
Among the footage was that of lean young man seen moving inside the bank with his face covered below his eyes with a handkerchief, District police sources said.
The bank caters to the needs of dozens of villages in Kundarapalli area and is popular among the local people.