Design of experiments (DOE) methods are very commonly used for process validation. In this study, we employed the Taguchi approach in order to develop an optimal process for the maximization of oscillatory shear stress environments (OSS). OSS has been associated with increase in cellular activity and has been linked to healthy gene expression and tissue formation. Therefore, OSS may be a key factor for many tissue-engineering applications. The results obtained through the Taguchi method identified the best combination of factors and levels associated with higher OSS. These conclusions were found to be in agreement with computational fluid dynamics (CFD) results that we previously found concerning optimal experimental set-up for OSS maximization.