There is a significant medical need for tough biodegradable polymer adhesives that can adapt to or recover from various mechanical deformations while remaining strongly attached to the underlying tissue. We approached this problem by using a polymer poly(glycerol-co-sebacate acrylate) and modifying the surface to mimic the nanotopography of gecko feet, which allows attachment to vertical surfaces. Translation of existing gecko-inspired adhesives for medical applications is complex, as multiple parameters must be optimized, including: biocompatibility, biodegradation, strong adhesive tissue bonding, as well as compliance and conformability to tissue surfaces. Ideally these adhesives would also have the ability to deliver drugs or growth factors to promote healing. As a first demonstration, we have created a gecko-inspired tissue adhesive from a biocompatible and biodegradable elastomer combined with a thin tissue-reactive biocompatible surface coating. Tissue adhesion was optimized by varying dimensions of the nanoscale pillars, including the ratio of tip diameter to pitch and the ratio of tip diameter to base diameter. Coating these nanomolded pillars of biodegradable elastomers with a thin layer of oxidized dextran significantly increased the interfacial adhesion strength on porcine intestine tissue in vitro and in the rat abdominal subfascial in vivo environment. This gecko-inspired medical adhesive may have potential applications for sealing wounds and for replacement or augmentation of sutures or staples.