An effective stabilizing system for PVC/clay composites has been established in this work. Different grades of Cloisite nano-clays supplied by Southern Clay Products Inc. were investigated. The effects of processing conditions on PVC/clay composite structure were investigated. The composite structure was characterized by both TEM and XRD. The particulate structure of PVC resin affected the distribution of clay, which could be improved by increasing the processing temperature. Almost fully exfoliated PVC/Cloisite 30B nano-composites were successfully prepared by a solution process in tetrahydrofuran, and the plasticizer migration resistance of this composite was significantly improved. Other commercial fillers for PVC such as calcium carbonate and hydrotalcite were compared with Cloisite 30B. It is interesting to find that PVC crystallization in the clay galleries can occur during annealing that increased the clay gallery spacing. There seemed to be orientation of the newly formed crystallites, and two types of orientation have been proposed.