We report a practical global deprotection of RNA 2'-O-tert-butyldimethylsilyl (TBS) ethers using commercially available aqueous NH(4)F. The procedure is applicable to both 96-well plate format and large-scale production of RNA. This improved procedure provides a safe, mild, and cost-effective alternative to highly hazardous Et(3)N x 3 HF, a reagent commonly used in the routine synthesis of RNA.