A 3D printable tissue adhesive is introduced as a promising alternative to sutures and staples for tissue repair, sealing defects, and immobilizing devices. This adhesive, developed through direct-ink-write 3D printing, offers tunable geometries and robust adhesion with wet tissues, achieving fluid-tight sealing in rat trachea and colon defect models. It is conformable, stretchable, and biocompatible, with a hydrophobic matrix enabling active sealing of bleeding tissues. The adhesive is composed of a poly(acrylic) acid (PAA)-functionalized N-hydroxysuccinimide ester (PAA-NHS ester) interpenetrated with a hydrophilic polyurethane (PU). The material is processed into a viscoelastic ink in a benign solvent, enabling extrusion-based 3D printing. The adhesive demonstrates high interfacial toughness, shear strength, and burst pressure when adhered to porcine skin. It is also mechanically tunable, allowing for anisotropic or nonlinear behavior through geometric parameters. In vivo studies show the adhesive is biocompatible, with mild inflammation and gradual degradation over four weeks. The 3D printable adhesive is effective in sealing tracheal and colon defects, and can be used for blood-resistant sealing in actively bleeding injuries. It also enables the fabrication of bioelectronic patches and drug delivery systems, demonstrating broad applicability in tissue-interfacing devices. The platform offers a scalable strategy for developing advanced tissue adhesive technologies with potential for application-specific designs.A 3D printable tissue adhesive is introduced as a promising alternative to sutures and staples for tissue repair, sealing defects, and immobilizing devices. This adhesive, developed through direct-ink-write 3D printing, offers tunable geometries and robust adhesion with wet tissues, achieving fluid-tight sealing in rat trachea and colon defect models. It is conformable, stretchable, and biocompatible, with a hydrophobic matrix enabling active sealing of bleeding tissues. The adhesive is composed of a poly(acrylic) acid (PAA)-functionalized N-hydroxysuccinimide ester (PAA-NHS ester) interpenetrated with a hydrophilic polyurethane (PU). The material is processed into a viscoelastic ink in a benign solvent, enabling extrusion-based 3D printing. The adhesive demonstrates high interfacial toughness, shear strength, and burst pressure when adhered to porcine skin. It is also mechanically tunable, allowing for anisotropic or nonlinear behavior through geometric parameters. In vivo studies show the adhesive is biocompatible, with mild inflammation and gradual degradation over four weeks. The 3D printable adhesive is effective in sealing tracheal and colon defects, and can be used for blood-resistant sealing in actively bleeding injuries. It also enables the fabrication of bioelectronic patches and drug delivery systems, demonstrating broad applicability in tissue-interfacing devices. The platform offers a scalable strategy for developing advanced tissue adhesive technologies with potential for application-specific designs.