The effectiveness and applicability of polyepoxysuccinic acid (PESA) as a reverse osmosis (RO) scale inhibitor were studied using static and dynamic methods. In the static study, PESA performed very well in the treatment of water samples with various types of scale that commonly exist in RO water (i.e., CaCO3, CaSO4, BaSO4, SrSO4), showing an average scale inhibition ratio of above 90% at a dosage of 10 mg/L. SEM analysis showed a disordered CaCO3 crystal in the presence of PESA, suggesting the scale-inhibiting mechanism. In the dynamic experiment, PESA also showed great performance in the treatment of 10 samples of synthetic tap water or sea water with different ion composition (i.e., Ca(2+), HCO3(-), Fe(3+), Al(3+)). After one cycle (7 d) of RO treatment of each sample at full recycle operation mode under a constant pressure of 1×10(6) Pa, the differences in water permeability and desalination ratio among samples are within 5%, suggesting that PESA is capable of treating waters of different quality, and has a strong resistance to ions that are harmful to scale inhibiting (i.e., Fe(3+) and Al(3+)). All these results suggest that PESA should be an effective scale inhibitor that is applicable to RO treatment of waters with a wide range of ion compositions.