Tianeptine (marketed as Coaxil or Stablon) is an atypical tricyclic drug used as an antidepressant in Europe, Asia, and Latin America. In the United States, tianeptine is not approved by the Food and Drug Administration (FDA) for medical use and is an unscheduled pharmaceutical agent* (1). Animal and human studies show that tianeptine is an opioid receptor agonist (2). Several case studies have reported severe adverse effects and even death from recreational abuse of tianeptine (3-5). To characterize tianeptine exposures in the United States, CDC analyzed all exposure calls related to tianeptine reported by poison control centers to the National Poison Data System (NPDS)† during 2000-2017. Tianeptine exposure calls, including those for intentional abuse or misuse, increased across the United States during 2014-2017, suggesting a possible emerging public health risk. Most tianeptine exposures occurred among persons aged 21-40 years and resulted in moderate outcomes. Neurologic, cardiovascular, and gastrointestinal signs and symptoms were the most commonly reported health effects, with some effects mimicking opioid toxicity. A substantial number of tianeptine exposure calls also reported clinical effects of withdrawal. Among 83 tianeptine exposures with noted coexposures, the most commonly reported coexposures were to phenibut, ethanol, benzodiazepines, and opioids.