Design of experiment provides a quality risk management to the manufacturing process of a product. This study was performed to select the water amount and identify the critical process parameters for wet granulation. Design of experiment, one of the quality by design approaches, was used in the study. The manufacturing process of valsartan and paravastatin fixed-dose combination tablets involves wet granulation, drying, sieving, blending and tableting. For wet granulation, a 3-factorial (granulating time, agitator speed and the amount of granulating water), 2-level (granule density and dissolution), 1-center (n = 3) point was used in the design of experiment batches and analyzed using Design Expert Software. Previously, this formulation was found to show good assay and content uniformity. Thus, only physical properties, bulk density and dissolution were evaluated for the design of experiment study. The amount of granulating water was identified as an important factor affecting the mean dissolution (p < 0.05) in contrast to the granulating time and agitator speed. Present results indicated that granulating time (6 to 10 min), amount of granulating water (40 to 60 g) and agitator speed (150 to 250 rpm) were optimal for wet granulation of valsartan and pravastatin fixed-dose combination tablets.