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Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent flares of nausea and vomiting, often with significant abdominal pain, of several days duration. Although traditional prophylactic and abortive treatments for CVS are often successful, a subset of CVS patients with chronic abdominal pain may not respond as well to standard therapies. This report is the first, to our knowledge, to describe the use of outpatient ketamine infusions as therapy for refractory CVS. We describe a 63-year-old woman with history of CVS who presented with abdominal pain and recurrent episodes of nausea and vomiting. She first received ketamine during an inpatient admission for a CVS flare, with the aim of treating the abdominal pain. Given her improvement, she was offered a series of outpatient ketamine infusions, which led to a significant reduction in her symptoms. Thus, ketamine may be useful as both an abortive and prophylactic therapy in CVS. Prior reports have noted the anti-emetic effects of ketamine in the perioperative setting, and there is emerging evidence for the use of ketamine infusions for the treatment of chronic pain. However, this report is the first to describe ketamine as a potential prophylactic treatment for CVS.