The phototoxicity of voriconazole (VN) prescribed in the treatment of severe fungal infections is frequently reported. Its major metabolite, a N-oxide derivative (VNO), was suspected to be the photosensitizer because it shows a maximum absorbance at ~310 nm in aqueous solutions. It was reported that the VNO photoproduct (VNOP) was phototoxic to human keratinocytes. Steady state and laser flash photolyses were performed to shed light on the phototoxic properties of VNO and VNOP. The quantum yield of the VNOP production by UVB-UVA light in buffered or alcoholic solutions is 0.6. VNOP has been identified as (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-7-oxa-1,3-diazabicyclo[4.1.0]hepta-2,4-dien-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol. VNOP undergoes a marked thermal degradation and an efficient UVA photolysis with well differentiated kinetics and end-products. The temperature-dependent VNOP dark degradation produces a single product VNOPD identified as 6-[(2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5-fluoropyrimidin-4-ol with absorbance maximum at 308 nm and ε = 2700 M cm. Under UVB-UVA irradiation, VNOPD, the stable end-product, is a remarkable photodynamic photosensitizer towards Trp and His. The Trp photo-oxidation (Φ(Trp) = 0.13) mainly involves type I radical reactions whereas His is oxidized by O (Φ(His) = 0.012). These results force us to question the validity of the in vitro photosensitization of human keratinocytes by VNO and VNOP previously reported.