The polymer supported phosphazene bases PS-P2tBu and the novel PS-P2PEG allowed for efficient extraction of [18F]F− from proton irradiated [18O]H2O and subsequent radiofluorination of a broad range of substrates directly on the resin. The highest radiochemical yields were obtained with aliphatic sulfonates (69%) and bromides (42%); the total radiosynthesis time was 35–45 min. The multivariate analysis showed that the radiochemical yields and purities were controlled by the resin load, reaction temperature, and column packing effects. The resins could be reused several times with the same or different substrates. The fully automated on-column radiofluorination methodology was applied to the radiosynthesis of the important PET radiotracers [18F]FLT and [18F]FDG. The latter was produced with 40% yield on a 120 GBq scale and passed GMP-regulated quality control required for commercial production of [18F]FDG. The combination of compact form factor, simplicity of [18F]F− recovery and processing, and column reusability can make solid phase radiofluorination an attractive radiochemistry platform for the emerging dose-on-demand instruments for bedside production of PET radiotracers.