The incorporation of leucine (Leu), a hydrophobic amino acid, into pharmaceutically relevant particles via spray-drying can improve the physicochemical and particulate properties, stability, and ultimately bioavailability of the final product. More specifically, Leu has been proposed to form a shell on the surface of spray-dried (SD) particles. The aim of this study was to explore the potential of Leu in the SD protein/trehalose (Tre) formulation to control the water uptake and moisture-induced recrystallization of amorphous Tre, using lysozyme (LZM) as a model protein. LZM/Tre (1:1, w/w) were dissolved in water with varied amounts of Leu (0 - 40 %, w/w) and processed by spray-drying. The solid form, residual moisture content (RMC), hygroscopicity, and morphology of SD LZM/Tre/Leu powders were evaluated, before and after storage under 22 °C/55 % RH conditions for 90 and 180 days. The X-ray powder diffraction results showed that Leu was in crystalline form when the amount of Leu in the formulation was at least 20 % (w/w). Thermo-gravimetric analysis and scanning electron microscopy results showed that 0 %, 5 %, and 10 % Leu formulations led to comparable RMC and raisin-like round particles. In contrast, higher Leu contents resulted in a lower RMC and increased surface corrugation of the SD particles. Dynamic vapor sorption analysis showed that in the 0 % Leu formulation, partial recrystallization of amorphous Tre to crystalline Tre·dihydrate occurred, and the addition of as little as 5 % Leu could inhibit the recrystallization of amorphous Tre during the water sorption/desorption cycle. In addition, after storage, formulations with higher Leu contents resulted in less water uptake. Rather than recrystallization of amorphous Tre in 0 %, 5 %, and 10 % Leu formulations, recrystallization of amorphous Leu was observed in both 5 % and 10 % Leu formulations after storage. In summary, our study demonstrated that the addition of Leu has the potential to reduce water uptake and inhibit moisture-induced recrystallization of amorphous Tre in the SD protein/Tre powder system.