Amyloidosis is characterized by extracellular deposition of protein fibrils in one or multiple organs. AA amyloidosis is secondarily occurred to be related with chronic infections or inflammatory diseases. We report a 67-year-old man suffered from secondary AA amyloidosis related with chronic Clostridium difficile colitis after repeated total hip replacement surgery. Infection control is the most important treatment of AA amyloidosis secondary to chronic infection. However, the patient's C. difficile colitis was not controlled well, eventually toxic megacolon with sepsis was developed. Consequently, he had to take total colectomy, but he expired with multi-organ failures. We suggested that early surgical procedure might be one option for intractable C. difficile colitis complicated with secondary amyloidosis.