Background: Long term abstinence from smoking is the objective of tobacco cessation therapy. Varenicline, FDA approved a novel beta 4 alpha 2 nAChR partial agonist may offer more benefits. Objectives: To assess the effectiveness and evidence of varenicline over nicotine replacement therapy in extended term abstinence to smoking. Search strategy: A systemic literature survey was carried out identify in electronic database such as PubMed, MEDLINE; Database of Reviews of Effects (DARE); in English language using MeSH terms ‘Varenicline’ ‘Nicotine Replacement Therapy’ ‘Abstinence’ of last 10 years from 2008 to 2020. Selection criteria: We included randomized controlled trials which compared Varenicline when compared with NRT. Results: Initially 182 articles were filtered out, selection of 7 articles by independent reviewer were done. Data from each study were extracted by one reviewer and independently checked for accuracy by a second reviewer. At two years, 28.8% of participants who were prescribed varenicline and 24.3 percent of those who were prescribed NRT quit; the adjusted odds ratio was 1.26 [95 percent confidence interval (CI): 1.23 to1.29], P 0.0001. At 24 weeks, the RR for varenicline versus NRT for abstinence was 1.25. (95 percent CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Conclusions: An 8-week course of varenicline tends to result in a higher rate of abstinence for up to three years than a similar course of NRT in clinical practice.