In this work, several novel poly-nadic-anhydride polyester plasticizers were developed to be used in poly(vinyl chloride) (PVC) film fabrication for the first time. Mechanical properties of the films, the compatibility of plasticizers in PVC resin, as well as testing of migration of the plasticizers, were performed in order to evaluate the efficiency of plasticization. Scanning electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry were used to characterize the unplasticized and plasticized polymer. The results demonstrated that the as-prepared poly-nadic-anhydride plasticized PVC film significantly improved the plasticization efficiency of PVC film based on the increase in the break in elongation of the films. According to scanning electron microscopy analysis, the poly-nadic-anhydride polyester plasticizers presented good compatibility with PVC resin. In volatility and extraction tests, PVC films plasticized with the poly-nadic-anhydrides showed enhanced migration resistance. The plasticizing effects induced by the poly-nadic-anhydride polyester plasticizers were also confirmed by a glass transition temperature shift toward lower temperatures in the plasticized films. J.