The influence of the roller compaction process on the granule quality of four different types of lactose showing different particle size, bulk density, crystallinity and morphology was compared by modeling. For each type of lactose the influence of the parameter settings on the friability was modeled by a second order polynomial having different average relative deviation values. Pressure, roll speed, vertical and horizontal screw speed were important parameters for all types of lactose but pressure was the most important parameter followed by the roll speed and the horizontal screw speed. Type, particle size and density had an influence on the usable roller compactor parameter settings. The best quality was obtained if at a high pressure a low horizontal screw speed was chosen for each roll speed. Roller compaction of spray-dried lactose was difficult. A gradual decrease of granule quality was seen for α-lactose monohydrate 200M, anhydrous β-lactose, α-lactose monohydrate 90M and spray-dried α-lactose, respectively. The roller compaction process using the different types of lactose was reproducible.