To determine the effect of pH, oxygen levels and ions on tetracycline oxidation and resultant discolouration. Solutions of demeclocycline hydrochloride or doxycycline hyclate were prepared and exposed to different pH conditions, pure oxygen or carbon dioxide, ascorbic acid or various ions (from calcium chloride, calcium nitrate, strontium chloride, magnesium chloride, zinc chloride, and bismuth nitrate). Subsequently, they were exposed to intense visible blue light (470±15nm) for 24h. Colour change was monitored using standardized digital photography. Parametric statistical analysis employing the Wilcoxon matched-pairs signed-rank test was performed to compare the mean change in different colour channels, assessing the discolouration effect of the modified conditions. An acidic pH reduced discolouration, whilst alkaline pH increased it. A higher oxygen tension resulted in more discolouration, as did the presence of calcium, strontium, and bismuth ions, all of which bind to tetracyclines. Conversely, zinc and magnesium ions had a mild photoprotective effect. Ascorbic acid, an anti-oxidant, reduced the level of discolouration. The tendency of these tetracyclines to undergo photo-oxidation is increased by common variables present in the clinical environment. There are potential benefits from using photoprotectors and anti-oxidants in these materials, to reduce the possibility of discolouration.