INTRODUCTION Over decades, smoking has been identified as one of the most preventable public health problems. However, rate of reduction in smoking prevalence has been relatively stagnant over the past decade. In parallel to the WHO Framework Convention on Tobacco Control (WHO FCTC) initiatives, quit smoking clinics (QSCs) have been established in various health clinics across Malaysia to proactively promote and aid smoking cessation amongst patients especially those with other comorbidities. The use of certain pharmacotherapy has been impeded by the cost in view of the higher pricing even though it may be more effective in aiding one to kick smoking habits. As such, it is pivotal for research to be conducted to evaluate both the efficacy and the cost of the interventions to determine the more cost-effective treatment regime. A retrospective study was conducted in Kuala Lumpur Health Clinic (KKKL) where medical records of patients who attended the QSC from January 2018 to December 2018 were evaluated. Cost estimation was done via macro and micro costing. The primary aim of this study was to evaluate the cost-effectiveness of combination therapy against monotherapy in smoking cessation program, hence providing evidence of the most effective intervention in the local setting. To predict the relationship between monotherapy and combination therapy on successful quitting, the treatment regimens were regressed on the outcome variables with a statistical significance set at a level of p<0.05. A total of 213 health records were evaluated and 94.8% were mainly male and 73.7% Malays. Majority of the samples (124 participants) were provided with combined therapy (nicotine and varenicline) and 89 participants were given monotherapy (nicotine only). It was found that none of the sociodemographic variables affects the outcome of quitting except for those with higher education level having significantly higher odds of quitting compared to those in the lower education level. Overall combination therapy was more effective in aiding smoking cessation (74.2% successful rate) compared to monotherapy (34.8% successful rate). Cost of treatment per patient for combination therapy was RM1,028.25, whereas for monotherapy was RM819.13. Cost- effectiveness ratio revealed that combination therapy is more cost-effective compared to monotherapy which cost per one percent successful rate was RM1,718 and RM2,095 respectively. In conclusion, combination therapy is more cost-effective compared to monotherapy in smoking cessation program conducted in Kuala Lumpur Health Clinic. Therefore, combination therapy should be the preferred choice for smoker to quit smoking compared to monotherapy. METHODOLOGY The study population consisted of 213 patients who had attended the smoking cessation clinic at KKKL in 2018. The general characteristics of the study population were mainly male dominated (94.8%) and Malays (73.7%). This was consistent with the current demographics of smokers in Malaysia. The mean ages of the smokers were similar in both the monotherapy and combination therapy arms, mainly aged above 40 years old. Treatment Outcome Analysis Treatment outcome was assessed by the number of successful smoking cessation as defined by smoke free for at least six months Treatment modalities and treatment outcome (N=213) Successful Not Successful Monotherapy 31 58 Combination Therapy 92 32 Total 123 90 Out of the 213 registered patients on pharmacotherapy, approximately two third of the patients have at least one comorbidity. Over one-third of them had either hypertension or diabetes with merely 3% of them have tuberculosis. Nevertheless, descriptive characteristics of the study population that was reported cessation outcome showed that none of the baseline characteristics have a clear-cut implication on success rate of smoking cessation. From the dataset, presence of different types of comorbidities did not statistically change the proportion of quit rate. Further ana