It is generally recognized that water, acting as a plasticizer, increases molecular mobility, leading to a decrease of the glass transition temperature (T_g) in amorphous systems. However, an anti-plasticizing effect of water was recently observed on prilocaine (PRL). This effect might be used in co-amorphous systems to moderate the plasticizing effect of water. Nicotinamide (NIC) can form co-amorphous systems with PRL. In order to investigate the effect of water on these co-amorphous systems, the T_gs and molecular mobility of hydrated co-amorphous NIC-PRL systems were compared with those of the respective anhydrous systems. Molecular mobility was estimated by considering the enthalpic recovery at the T_g using the Kohlrausch-Williams-Watts (KWW) equation. At molar ratios of NIC above 0.2, a plasticizing effect of water on co-amorphous NIC-PRL systems was observed with increasing the NIC concentration. In contrast, at molar ratios of NIC of 0.2 and below, water had an anti-plasticizing effect on the co-amorphous NIC-PRL systems, with increased T_gs and reduced mobility upon hydration.