Water is generally regarded as a universal plasticizer of amorphous drugs or amorphous drug-containing systems. A decrease in glass-transition temperature (T-g) is considered the general result of this plasticizing effect. A recent study exhibits that water can increase the T-g of amorphous prilocaine (PRL) and thus shows an anti-plasticizing effect. The structurally similar drug lidocaine (LID) might show similar interactions with water, and thus an anti-plasticizing effect of water is hypothesized to also occur in amorphous LID. However, the influence of water on the T-g of LID cannot be determined directly due to the very low stability of LID in the amorphous form. It is possible to predict the T-g of LID from a co-amorphous system of PRL-LID using the Gordon-Taylor equation. Interactions were observed between PRL and LID based on the deviations between the experimental T(g)s and the T(g)s calculated by the conventional use of the Gordon-Taylor equation. A modified use of the Gordon-Taylor equation was applied using the optimal co-amorphous system as a separate component and the excess drug as the other component. The predicted T-g of fully hydrated LID could thus be determined and was found to be increased by 0.9 +/- 0.7 K compared with the T-g of water-free amorphous LID. It could be shown that water exhibited a small anti-plasticizing effect on LID.