INTRODUCTION: In 2015, smoking prevalence in Republic of Macedonia was 36% in men and 21% in women We aim to assess the effectiveness and cost-effectiveness of two methods of motivating smokers to quit smoking compared with very brief advice (VBA) alone. Тo date, there are no studies investigating smoking cessation treatment in Republic of Macedonia. METHODS/DESIGN: RCT with process evaluation and cost-effectiveness analysis within 31 general practices in Republic of Macedonia recruiting smokers currently smoking >10 cigarettes per day, aged >35 years, attending primary care practices for any reason, regardless of motivation to quit smoking. Respondents will be randomized into one of three groups: (1) VBA and assessment and communication of lung age; (2) VBA and additional assessment and communication of exhaled carbon monoxide (CO) levels; or (3) control group – VBA. All participants who attempt to quit smoking will be offered behavioral support based on the UK standard program for smoking cessation. Primary outcome: Proportion of smokers who are quit at 4 weeks (7-day point prevalence, confirmed by salivary cotinine level). Secondary outcomes: Proportion who have attempted to quit smoking or have quit smoking, a proportion that has reduced the number of cigarettes and motivation to quit smoking; cost-effectiveness analysis calculating cost per quality-adjusted life year. We will evaluate the fidelity to the intervention and will explore patients’ and GPs’ experience and the acceptability of the study intervention by interview. DISCUSSION: The study will evaluate the effectiveness of combining feedback about lung age or exhaled CO levels with VBA and support for smoking cessation in primary care compared to giving VBA and support alone. It will explore how willing primary care physicians are to perform such interventions and the acceptability and effectiveness of such interventions to patients in Republic of Macedonia. TRIAL REGISTRATION: The study is registered on the ISRCTN registry (ISRCTN54228638).