Varenicline represents a major advance in the treatment of nicotine addiction and has been shown to be safe and effective to promote abstinence. However, in a small number of patients, neuropsychiatric adverse events and worsening of underlying psychiatric conditions have been reported. As the veteran population has higher rates of co-morbid psychiatric conditions and nicotine dependence this population may be at higher risk for serious adverse effects to varenicline warranting close monitoring. Herein we report seven cases of varenicline associated neuropsychiatric adverse events and describe an institutional response to adequately monitor patients to ensure safety and efficacy.