Background: Estimating the burden of non-communicable diseases particularly cardiovascular disease (CVD) is essential for health management and policymaking. In this paper, we used a regression model to estimate the future impact of demographic changes on the burden of CVD in Iran during the next two decades. Methods: Disability-adjusted life years (DALY) were used to estimate the future burden of CVD in Iran. A regression model was used to estimate DALY caused by CVD in the Iranian population aged 30–100 yr, stratified by age group and sex. The predicted population of Iranians aged ≥ 30 yr was entered into the model and DALY were calculated over 2005-2025. To assess the areas of uncertainty in the model, we did sensitivity analysis and Monte Carlo Simulation. Results: In the year 2005, there were 847309 DALYs caused by CVD in Iranian adults aged ≥ 30 yr. This figure will nearly be 1728836 DALYs in 2025. In other words, just because of the aging, DALY related to CVD will increase more than two-fold in 2025 compared with 2005. The burden of CVD was higher in men (443235) than in women (404235) in 2005; but in 2025, the difference will be less (867639 vs. 861319). Conclusion: The burden of CVD will increase steeply in Iran over 2005–2025, mainly because of the aging population. Therefore, more attention is needed to deal with the impact of CVD in the following decades in Iran.