We report two cases of hepatotoxicity induced by mirtazapine. Two women treated for depression with mirtazapine developed severe hepatotoxicity because of the drug. In the first case, mirtazapine was prescribed for 3 years and the patient developed derangement in liver function with prolonged jaundice, which improved after the withdrawal of mirtazapine. The use of mirtazapine in the second case was associated with prolonged jaundice, which only recovered 3 months after the withdrawal of mirtazapine. The cause of mirtazapine-induced liver toxicity was unknown, and to our knowledge, these are the first reported cases of mirtazapine-induced prolonged jaundice.