The present study investigates CFD simulation of aqueous-organic two phase flow in microreactors with a guideline structure. The guideline structure was developed in order to stabilize and to maintain parallel flow of liquids within the microreactors. The CFD simulation can well predict the flow patterns observed in experiments. Upon determining the flow pattern and stability, it is reported that, with the presence of guideline structure, the interface became more curved and stable. Finally, the role of the guideline structure on the flow development was also investigated.