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Background: IraPEN, a program developed in Iran based on the World Health Organization (WHO) package of essential noncommunicable (PEN) disease interventions for primary healthcare, was launched in 2015. Preventive interventions for cardiovascular diseases (CVDs) are based on the level of risk calculated using the WHO CVD risk chart., Objective: The main objective of this study was to measure the potential cost-effectiveness (CE) of IraPEN preventive actions for CVD in comparison with the status quo ., Methods: A CE analysis from a healthcare perspective was conducted. Markov models were employed for individuals with and without diabetes separately. Based on the WHO CVD risk chart, four index cohorts were constructed as low (<10%), moderate (10%-19%), high (20%-29%), and very high risk (≥30%). Life years (LY) gained and quality-adjusted life years (QALY) were used as the outcome measures., Results: The intervention yields an incremental cost-effectiveness ratio (ICER) of $804, $551, and -$44 per QALY for moderate, high, and very high CVD risk in groups without diabetes, respectively. These groups gained 0.69, 0.96, and 1.45 LY, respectively, from the intervention. The results demonstrated an ICER of $711, $630, -$42, and -$71 for low, moderate, high, and very high-risk groups with diabetes, respectively, while they gained 0.46, 1.2, 2.04, and 2.29 years from the intervention., Conclusion: The IraPEN program was highly cost-effective for all CVD risk groups in the individuals without diabetes except the low-risk group. The intervention was cost-effective for all patients with diabetes regardless of their CVD risk. The results demonstrated that the IraPEN program can likely provide substantial health benefits to Iranian individuals and cost savings to the national healthcare provider., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jamshidi, Daroudi, Aas and Khalili.)