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In this work, the use of an environmentally friendly plasticizer derived epoxidized cottonseed oil (ECSO) for poly(lactic acid) (PLA) is proposed. Melt extrusion was used to plasticize PLA formulations with different ECSO contents in the 0–10 wt.%. PLA formulation with 10 wt.% shows a remarkable increase in mechanical ductile properties with a percentage increase in elongation at break of more than 1100% and a noticeable increase in the impact absorbed energy. Differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA) revealed a clear decrease in the glass transition temperature of neat PLA as the ECSO content increased. Field emission scanning electron microscopy (FESEM) of fractured surfaces from impact tests showed an improvement of ductility with typical rough and porous topographies. Migration tests in n -hexane at different temperatures revealed very low migration properties thus leading to new interesting plasticizers for improved PLA industrial formulations. [ABSTRACT FROM AUTHOR]