BACKGROUND: The aim of this study was describing the sampling methods and sample size of the Isfahan Healthy Heart Program (IHHP) and its sub-studies in focus.METHODS: The IHHP was carried out between 2000 and 2007 in urban and rural areas in 3 districts, namely Isfahan and Najafabad (as the intervention areas), and Arak (as the reference area), Iran. It consisted of the 3 phases of baseline surveys during 2000-2001, interventions between 2002 and 2005, and post-intervention surveys during 2006-2007 on 4 target groups (adults, health professionals, cardiac patients, children, and adolescents). During 2002 to 2005, 4 evaluation studies were conducted to evaluate short-term results. An ongoing cohort study entitled the Isfahan Cohort Study was performed on those aged ≥ 35 years at baseline in 2001 to access the risk of cardiovascular disease (CVD) occurrence.RESULTS: Using stratified random cluster methods, 12514, 5891, 4793, 6096, 3012, and 9572 adults and 1946, 1999, 1427, 1223, 389, and 1992 adolescents were chosen in the 1st to 3rd phases. Furthermore, simple random sampling was used for selecting 923, 694, 1000, and 2015 health professionals and 814, 452, 420, and 502 cardiac patients. A multistage sampling method was adopted for the collection of samples from parents of preschoolers and primary school children aged 2-10 years, adolescents’ parents, and some teachers. A prospective cohort study was started on 6504 eligible individuals.CONCLUSION: The IHHP, as a comprehensive community-based interventional trial in Iran, among the few population-based studies around the world, has reasonable sampling methods and sample size.