• Ionic liquids (ILs) effectively enhance the relative volatility of 1,3,5-trioxane (TOX) to water, enabling the destruction of the azeotrope at an IL mole fraction of about 0.10.
• The addition of ILs increases TOX volatility while decreasing water volatility, with the effect intensifying at higher IL dosages.
• The NRTL model successfully correlates experimental VLE data, revealing strong IL–water interactions that drive the separation enhancement.
• ILs with strong polarity and hydrophilicity are identified as promising additives for improving TOX concentration in the vapor phase, offering potential energy savings in industrial separation.