The influence of particle size of MCC, as a binder, and theophylline, as an active pharmaceutical ingredient on the process of roll compaction/dry granulation was investigated using a D-optimal design of experiments. Examined parameters were particle size of both starting materials, fraction of theophylline and ribbon porosity. Therefore, different binary mixtures were roll compacted, dry granulated and compressed into tablets. Flowability of powders and granules and tensile strength of tablets made from powders or granules were the focus of this study. This study showed that a decrease in particle size of MCC or theophylline resulted in an increase of tensile strength even after roll compaction/dry granulation. Comparing tensile strength of tablets made from powder using large size MCC with ones made from granules with small sized MCC revealed that the tensile strength of tablets produced from granules was equal or even higher than tensile strength from direct compressed tablets. Furthermore, using small sized MCC instead of large sized MCC led to larger granules with better flowability. It is shown that the fraction of binder can be reduced without a loss of tensile strength of the final tablets by size reduction of MCC.