Herein, we publish data from regulatory studies investigating the oral ADME (absorption, distribution, metabolism, excretion) of tricyclazole in vivo, in silico and in vitro. The oral route is relevant to human dietary exposure assessment. Tricyclazole is readily absorbed and highly bioavailable in rodents (>86%) with indication of saturation of absorption at high doses. Enterohepatic recirculation is evident. Excretion occurs quickly both via urinary (31–64%) and faecal routes (39–65%), with substantial biliary elimination in the rat (≥58%). The tricyclazole-derived radioactivity is distributed to major organs, including those investigated in in vivo genotoxicity studies (liver, kidney, gastrointestinal tract and bone marrow). There is no evidence of bioaccumulation. Metabolism is extensive (approximately 30 metabolites), with the liver being identified as the primary metabolism organ with Phase I and II enzymes involved. Several metabolites are formed following an initial cleavage of the central thiazole ring, with no loss of free triazole from the remaining phenyl ring. A group of 4 metabolites derive from an initial oxidation step with the formation of the tricyclazole-alcohol, a relevant crop metabolite, and account for up to 13% of the administered dose. In vitro metabolism, investigated with liver microsomes, confirmed that humans do not form unique metabolites.