<p>Due to the tendency of plasticizers like di-2-ethylhexyl phthalate (DOP) and bis(2-ethylhexyl)adipate (DOA) to migrate from PVC products, which pose serious health risks, and have therefore been increasingly restricted in many countries. Enhancing the migration resistance of plasticizers in PVC remains a critical challenge. Based on the molecular design concept of plasticizers, ester-branched epoxidized oleic acid plasticizers (E-ECD, E-EOD, and E-EHD) with excellent migration resistance in PVC were synthesized through esterification, Claisen condensation, and epoxidation reactions. The structural characteristics of the synthesized plasticizers were determined using FT-IR and ¹H NMR. During a 10-day migration resistance test, PVC plasticized with E-ECD exhibited a weight loss of less than 5 wt% in both polar and non-polar environments, with a migration rate of only 0.6 wt% in oily media. The potential plasticizing mechanisms of these plasticizers in PVC are elaborated in detail. This study offers a practical and generalizable strategy for the development of high-performance plasticizers with improved migration resistance.</p> Graphical abstract <p></p>