In this paper, we demonstrate that the hydrophobic ionic liquid (IL) such as 1-hexyl-3-methyl imidazolium hexafluorophosphate, [hmim][PF6], with silver salt, e.g. AgBF4, is an excellent extraction phase to separate and enrich omega-3 polyunsaturated fatty acid methyl esters (PUFAMEs) from the mixed solution containing closely related saturated, monounsaturated or diunsaturated fatty acid methyl esters. With this silver salt-ionic liquids extraction phase, the health-beneficial omega-3 PUFAMEs such as methyl ester of all-cis-5,8,11,14, 17-eicosapentaenoic acid (20:5 or EPA) and methyl ester of all-cis-4,7,10,13,16, 19-docosahexaenoic acid (22:6 or DHA) were largely enriched from 18% (wt %) in the original cod liver oil to greater than 80% in the 1-hexene stripping solvent. The unique properties of nonvolatility and adequate polarity allow ILs to dissolve or suspend silver salts and to be conveniently adopted as extraction phase in separating PUFAMEs. The ILs with different hydrophobicities and different silver salts were screened to obtain an optimal combination of IL and silver salt with the highest extraction capability and selectivity. The screening results showed that AgBF4 exhibited high extraction capability in the hydrophobic ILs but little or no extraction capability in the hydrophilic ILs. Furthermore, the high extraction capability of AgBF4 in hydrophobic ILs was much greater than that of AgBF4 in traditional silver-water or silver-alcohol extraction systems. Pretreating the silver-ILs extraction phase with steric hindered short chain olefins could significantly enhance its extraction selectivity for PUFAMEs. Nine runs of the IL-silver extraction phase showed no obvious decrease in its extraction capabilities and selectivities.