Background: Critical inter-provincial differences within Iran in the pattern of noncommunicable diseases (NCDs) and difficulties inherent to the identification of prevention methods to reduce mortality from NCDs have challenged the implementation of the provincial health system plan. The Shahrekord Cohort Study was designed to address these gaps in Chaharmahal and Bakhtiari, a province of high altitude of the southwest of Iran, characterized by its large Bakthiari population.Methods: This ongoing cohort, prospective longitudinal study is a unique, rich biobank and a large-scale study conducted for the first time in Chaharmahal and Bakhtiari province in Iran. The study began in 2015, recruited 10075 participants (52.8% female) from both urban and rural (30.2%) areas and participants will be followed up until at least 2035. Diseases and their outcomes are ascertained from clinical examinations, interviews, and linkage with medical records registered in the health system.Results: Preliminary results indicate that the prevalence of NCDs at baseline was relatively high, for example 10.7% for type 2 diabetes mellitus, 20.2% for hypertension, 14.6% for non-alcoholic fatty liver, 11.4% for thyroid disease, and 5.7%, 0.9% and 1.3% for ischemic heart disease, stroke and myocardial infarction respectively. The mean (standard deviation) of BMI, systolic blood pressure, fasting blood glucose and cholesterol were 27.6 (4.6) kg/m2, 115.4 (17.3) mmHg, 96.7 (27.3) mmol/L and 184.1 (42.8) respectively. All NCDs appeared to be more frequent in urban than rural areas, except gastroesophageal reflux (32.3% in rural and 29% in the urban area). Conclusions: The Shahrekord Cohort Study provides a platform for epidemiological studies that will be useful for a better prevention and management of NCDs in the southwest of Iran.