PURPOSE: Alcohol dependence is a public health problem worldwide, commonly associated with withdrawal symptoms for which diazepam is a frequently used drug. We studied the effect of CYP2C19 gene polymorphisms on diazepam loading dose requirement and time to reversal of acute alcohol withdrawal symptoms. We also studied the influence of the polymorphism in this gene on the persistent symptoms after loading dose of diazepam. METHODS: Sixty-nine patients who reported to the psychiatry department with symptoms of alcohol withdrawal diagnosed by DSM-IV criteria were included for the study. A 10-mg loading dose of diazepam was administered iv after baseline assessment of withdrawal severity using CIWA-Ar scoring. The patients were assessed for improvement of the symptoms every two hourly and 20 mg oral diazepam was given based on improvement of symptoms. Genotyping for CYP2C192, CYP2C193 and CYP2C19*17 was done by PCR-RFLP and RT-PCR methods. RESULTS: The diazepam dose requirement as well as the time required for reversal of acute symptoms was not statistically different among the different genotype groups. Similarly, the frequency of patients with persistent symptoms after successful treatment of the acute episode was not different among the groups. However, the total diazepam dose requirement was influenced by baseline CIWA-Ar scores (adjusted OR 0.21, p = 0.026). In addition, the odds of treatment with a lower dose (10 mg) of diazepam were higher in smokers (adjusted OR 5.22, p = 0.025) and patients with other addiction (adjusted OR 9.26, p = 0.026). CONCLUSION: We found that CYP2C19 polymorphism did not have any significant effect on the diazepam dose requirement, time duration needed for successful treatment or on the persistent symptoms after loading dose of diazepam in South Indian population. However, diazepam dose requirement was influenced by baseline CIWA-Ar score, smoking status and other comorbid addictions.