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Drug-induced liver injury is a serious adverse drug reaction that can result in acute liver injury or cholestatic injury affecting the bile ducts, known as cholangiopathic liver injury (CLI). Although CLI is not as familiar as the hepatocellular pattern, emerging evidence suggests that it may occur after coronavirus disease 2019 (COVID-19) vaccination. This case report focuses on an 89-year-old woman who developed CLI after receiving the tozinameran COVID-19 vaccine. The main aim of this report was to raise awareness of the possibility of developing CLI after COVID-19 vaccination and to underscore the critical significance of promptly identifying and managing this infrequent but severe side effect.