The mechanism of photo-oxidation of tryptophan (Trp) sensitized by riboflavin (RF) was examined employinghigh concentrations of Trp and RF, with a high intensity 365 nm light emitting diode (LED) source under N2,20% and 100% O2atmospheres. Dimerization of Trp was a major pathway under the N2atmosphere, though thisoccurred with a low yield (DφTrp= 5.9 × 10−3), probably as a result of extensive back electron transfer re-actions between RF•-and Trp(H)•+. The presence of O2decreased the extent of this back electron transfer re-action, and the extent of Trp dimerization. This difference is attributed to the formation of O2•-(generated viaelectron transfer from RF•-to O2) which reacts rapidly with Trp•leading to extensive consumption of the parentamino acid and formation of peroxides and multiple other oxygenated products (N-formylkynurenine, alcohols,diols) of Trp, as detected by LC-MS. Thus, it appears that thefirst step of the Type 1 mechanism of Trp photo-oxidation, induced by this high intensity 365 nm light source, is an electron transfer reaction between the aminoacid and3RF, with the presence of O2modulating the subsequent reactions and the products formed, as a resultof O2•-formation. These data have potential biological significance as LED systems and RF-based treatments havebeen proposed for the treatment of pathological myopia and keratitis.