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Abstract Wound closure in surgeries is traditionally achieved using invasive methods such as sutures and staples. Adhesion‐based wound closure methods such as tissue adhesives, sealants, and hemostats are slowly replacing these methods due to their ease of application. Although several chemistries have been developed and used commercially for wound closure, there is still a need for better tissue adhesives from the point of view of toxicity, wet‐adhesion strength, and long‐term bonding. Catechol chemistry has shown great promise in developing wet‐set adhesives that meet these criteria. Herein, we have studied the biocompatibility of a catechol‐based copolymer adhesive, poly([dopamine methacrylamide]‐co‐[methyl methacrylate]‐co‐[poly(ethylene glycol) methyl ether methacrylate]) or poly(catechol‐MMA‐OEG), which is soluble in water. The adhesive was injected subcutaneously in a mouse model on its own and in combination with a sodium periodate crosslinker. After 72 h, 4 weeks, and 12 weeks, the mice were euthanized and subjected to histopathological analysis. Both adhesives were present and still palpable at the end of 12 weeks. The moderate inflammation observed for the poly(catechol‐MMA‐OEG) cohort at 72 h had reduced to mild inflammation at the end of 12 weeks. However, the moderate inflammatory response observed for the poly(catechol‐MMA‐OEG) + crosslinker cohort at 72 h had not subsided at 12 weeks.