16α-[(18)F]fluoroestradiol ([(18)F]FES) is known as a clinically important tracer in nuclear medicine as an estrogen receptor ligand for investigating primary and metastatic breast cancers. Synthesizing [(18)F]FES is a two-step process associated with [(18)F]fluoride incorporation to the precursor (3-methoxymethyl 16β,17β-epiestriol-O-cyclic sulfone) and subsequent hydrolysis of the [(18)F]fluorinated intermediate with 2 N HCl. The impact of microwave (MW) heating on both fluorination and hydrolysis reactions was investigated. The duration and temperatures of the fluorination reaction were varied for both MW heating and conventional heating (CH) methods. Chemical and radiochemical purity and radiochemical yields were investigated for CH and compared with MW-assisted radiosyntheses. Quality control tests of MW-assisted [(18)F]FES were performed following US Pharmacopeia procedures for clinical-grade positron emission tomography pharmaceuticals. The results demonstrate that microwaving not only improves the (18)F-fluoride incorporation (~55% improvement at 110°C for 4 min) but also significantly reduces hydrolysis time (approximately sevenfold reduction at 120°C) in comparison with CH under similar conditions. The overall isolated radiochemical yield of purified [(18)F]FES was significantly higher (~90% improvement) with MW, and side products were notably fewer. Quality control test results demonstrated that [(18)F]FES produced by microwaving was suitable for human injection.