Arsenic trioxide has been used successfully for the treatment of refractory acute promyelocytic leukemia and has shown promise in the treatment of myelodysplastic syndrome (MDS), although it is not a labeled indication. Retinoic acid syndrome is manifested by fever, dyspnea, peripheral edema, pulmonary infiltrates, and pleural and/or pericardial effusions and is typically seen in conjunction with all- trans retinoic acid therapy of acute promyelocytic leukemia. We report a case of acute lung injury and a retinoic acid syndrome-like illness in a patient who received arsenic for MDS. To our knowledge, this is the first such report, and clinicians should be aware of this potentially life-threatening complication of arsenic trioxide treatment in patients with MDS.