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There are different modalities for management of Nicotine dependence, but it is still inconclusive which is the best modality for the treatment of Nicotine dependence syndrome (NDS). In this background the present study was carried out to assess the efficacy and to compare different modalities for the treatment of NDS. Methods Patients diagnosed as NDS as per ICD-10 were taken up for study. These patients were administered proforma to elicit sociodemographic details, Fagerstrom test for Nicotine Dependence, Questionnaire of Smoking Urges-Brief and breath analysis was done using carbon monoxide meter. Assessment was done at base line and at weekly follow-ups for 12 weeks. Patients were divided into six groups randomly. Group A received BUP at a dose of 150 mg/day for 3 days; subsequently increased to 300 mg/day, Group B: for initial 6 weeks Nicotine gum of 4 mg every 1–2 hourly was used and next 6 weeks every 2–4 hourly was used, Group C: BI, Group D: BI + BUP, Group E: BI + NRT, Group F received BUP + NRT + BI. Results The quit rates at end of the study were BUP-30%, NRT-26.66%, BI-23.33%, BI + BUP-43.33%, BI + NRT-33.33%, and BI + BUP + NRT-50%. BI + BUP + NRT had 2–3 times more quit rates than the individual modality treatment group. Conclusion There was no statistically significant difference between the study groups, but there was clinical difference in quit rates. Among the groups BI + BUP + NRT had higher quit rates compared to other groups. Combination modalities yield better quit rates than individual modalities. [ABSTRACT FROM AUTHOR]