OBJECTIVES: The main objective was to evaluate the cost-effectiveness of various medical therapy combinations in managing chronic coronary syndrome (CCS) in Iran, based on real-world and patient-level data. DESIGN: A cost-utility analysis employing a Markov model was conducted using data from a retrospective cohort study. SETTING: The study was conducted in the healthcare setting of Iran, focusing on primary and secondary care. PARTICIPANTS: Patients with CCS were included in the study. Numbers entering and completing the study were reported, with clear definitions of selection, entry and exclusion criteria. INTERVENTIONS: All combinations of recommended medical therapies for CCS were permitted. Ultimately, taking into account the sample size and study power, a comparison was made between the combination therapy of β-blockers (BB), long-acting nitroglycerin (LAN), aspirin (ASA) and statin versus the group receiving only BB, ASA and statin. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the incremental cost-effectiveness ratio, along with an initial evaluation of disability-adjusted life-years (DALYs) and costs related to the interventions. RESULTS: The BB/LAN/ASA/statin combination was cost-saving and effective, averting 0.02 DALYs and saving 72 compared with BB/ASA/statin. This combination was cost-effective in over 97% of the probabilistic sensitivity analysis results. CONCLUSIONS: Incorporating LAN into the combination therapy of BB, ASA and statin is cost-effective in Iran. This finding provides evidence for policymakers on resource allocation in low-income countries.