Acetaminophen overdose can lead to severe liver and kidney failure; however, the risk of therapeutic doses in healthy individuals causing acute kidney injury (AKI) is less clear. We herein describe the cases of two young adults with renal biopsy-proven acute tubular necrosis under a therapeutic dose of acetaminophen. The first patient exhibited mild reversible renal insufficiency, whereas, in the second case, the patient demonstrated a slightly increased serum creatinine level and enlarged kidneys and the administration of contrast media and antibiotics may have worsened the renal dysfunction, leading to the need for temporal hemodialysis. Physicians should be aware of the risk of acetaminophen causing AKI and avoid administering other nephrotoxic agents in such cases.