The Baylis–Hillman reaction of HMF was investigated in various bio-based solvent systems and in water. Although pure water is able to promote the reaction, aqueous mixtures with ethanol, isopropanol, methyl-THF (MeTHF), tetrahydrofurfuryl-alcohol (THFA) show better overall efficacy for the HMF Baylis–Hillman reaction than pure water or the pure bio-based solvent. Such solvent systems can replace THF or dioxane, often used for BH reactions. However, pure bio-based solvents can be used in the case of the more polar glucosyloxymethylfurfural (GMF). These results show that the most appropriate medium must also take into account the polarity of the starting aldehyde.