Coffinite, USiO4, is the second most abundant U4+ mineral on Earth, and its formation by the alteration of the UO2 in spent nuclear fuel in a geologic repository may control the release of radionuclides to the environment. Despite its abundance in nature, the synthesis and characterization of coffinite have eluded researchers for decades. On the basis of the recent synthesis of USiO4, we can now define the experimental conditions under which coffinite is most efficiently formed. Optimal formation conditions are defined for four parameters: pH, T, heating time, and U/Si molar ratio. The adjustment of pH between 10 and 12 leads probably to the formation of a uranium(IV) hydroxo-silicate complex that acts as a precursor of uranium(IV) silicate colloids and then of coffinite. Moreover, in this pH range, the largest yield of coffinite formation (as compared with those of the two competing byproduct phases, nanometer-scale UO2 and amorphous SiO2) is obtained for 250 degrees C, 7 days, and 100% excess silica.