As a pyrimidine analog with potent and sustained antiviral activity against hepatitis B virus, clevudine has been known to have no effect on mitochondrial structure, DNA content, or function. There is little information on the side effects of clevudine, which has not been approved for the treatment of chronic hepatitis B outside of South Korea. We report here two cases of chronic hepatitis B patients who experienced mitochondrial myopathy after clevudine medication. These cases raise concerns about the safety profile of clevudine for the treatment of chronic hepatitis B.