OBJECTIVES: To determine the cost-effectiveness of smoking cessation interventions that available in the Malaysian healthcare setting. METHODS: A decision analytic model was developed to describe the economic consequences upon using different smoking cessation interventions (i.e. counselling only, counselling with varenicline, counselling with NRT and counselling with varenicline and NRT). Outcome probabilities (i.e. treatment success, treatment failure) were obtained from an observational study, involving 334 participants from 11 health clinics in Kuala Lumpur and Putrajaya, Malaysia. The analysis was performed from the healthcare provider perspective. Direct medical costs were included in the analysis, using the latest resource from the Ministry of Health, Malaysia. The model outcome [i.e. incremental cost-effectiveness ratio (ICER) per 6-month abstinent rate] was determined if an intervention was found to be more effective at a higher cost when compared to the other comparator. Probabilistic sensitivity analysis was conducted using Monte Carlo simulation. RESULTS: Smoking cessation interventions (i.e. counselling with varenicline and counselling with NRT) were found to be cost-effective. Combination of varenicline, NRT and counselling was dominated by counselling only group. The ICERs per 6-month abstinence rate for counselling with varenicline and counselling with NRT were RM2,317.20 (USD583.61) and RM5,020.85 (USD1,264.55) respectively. The ICERs per 6-month abstinence rate were most sensitive to the cost of patients with treatment failure in the counselling with varenicline arm and the probability of patients succeeded with counselling and NRT. The probability of both interventions (i.e. counselling with varenicline and counselling with NRT) being a cost-effective option for smoking cessation was above 99.9%. CONCLUSIONS: Counselling with varenicline appeared to be the most cost-effective smoking cessation intervention from the Malaysian healthcare perspective.