The effect of whey protein-to-casein ratio (60:40, 50:50 and 40:60) on the physicochemical properties of model infant milk formula (IMF) wet-mixes and powders prepared therefrom was studied. A lower whey protein-to-casein ratio lowered the zeta potential and apparent viscosity of wet-mixes and increased the particle size after evaporation. Particle size and water activity of powders decreased with decreasing whey protein-to-casein ratio. Glass transition temperature, crystallinity, surface free fat content and solubility of the powders were similar and unaffected by protein composition. Surface composition of powders was substantially different from their bulk composition irrespective of the protein ratios, with fat representing more of the powders surface (∼42–44%) followed by protein (∼30–32%) and lactose (∼24–26%). Overall, IMF powders can be prepared by varying the whey protein-to-casein ratio without affecting the physicochemical properties of the feed and the spray-dried powders.