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Tuberculosis is a leading cause of mortality worldwide due to infection diseases. Isoniazid is the first line drug therapy for prophylaxis and treatment of tuberculosis. Isoniazid may cause neurologic side effects including peripheral neuropathy, convulsions and ataxia and psychiatric side effects including euphoria and psychosis. We report here a case with acute psychotic symptoms in the course of prophylactic isoniazide treatment. A 53-year-old woman referred to outpatient clinic and hospitalized with persecution and reference delusions and agitation. She did not have a psychiatric history except some short-term conversion symptoms seen especially in stressful conditions. In addition, she had no history of systematic disease and substance use. Her husband was diagnosed pulmonary tuberculosis 3 months ago and isoniazide 150 mg/day treatment was started as prophylaxis to the patient. In the tenth week of isoniazide therapy, she was anxious and had some preoccupations about her husband’s disease. She was referred to a psychiatrist for her anxiety and negative thoughts and sertraline and hydroxyzine was prescribed. She experienced tremor after first use of these medications, and denied to use anymore because the thoughts of poisoning by her son and daughter-in-law. In her mental status examination, reference and persecution delusions and agitation were observed. MMSE score was 26. Isoniazide was discontinued and risperidone 2 mg/day treatment was given. Her symptoms resolved completely within a week. In her outpatient follow up visits, no psychotic symptoms were observed during 11 months. In the evaluation of patients with acute psychotic symptoms, some characteristics may suggest psychosis caused by medical conditions: late onset (>40), co-occurring systematic diseases and medication use, lack of negative symptoms and cognitive deficits. Neuropsychiatric symptoms related to isoniazide can develop days or months after initiation of isoniazide treatment. If psychotic symptoms are thought to be related to isoniazide, it should be discontinued. In some cases, it was reported that psychotic symptoms were relapsed after reintroduction of isoniazide and it may be more severe. Atypical antipsychotics were reported to be effective in the treatment of isoniazide induced psychotic symptoms.