A new preparation of [18F]fluoromisonidazole [1H-1-(3-[18F] fluoro-2-hydroxypropyl)-2-nitroimidazole] is presented as a two-step, two-pot reaction sequence. The method is useful for the production of 20-30 mCi quantities of this compound from [18F]fluoride, available in 40% radiochemical yield at end of bombardment (EOB) with a specific activity (nca) of greater than 650 Ci/mmol (EOB) and a synthesis time of approximately 140 min. The key feature of the reaction scheme is the preparation of a new fluoroalkylating agent, [18F]epifluorohydrin.