Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the self-replenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectious bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella salina, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.