Non-communicable diseases (NCDs) account for 76% of deaths in Iran and this number is on the rise, parallel to global rates. Many risk factors associated with NCDs are preventable; however it is first necessary to conduct observational studies to identify relevant risk factors, and the most appropriate approach to control them. Iran is a multi-ethnic country, therefore the Ministry of Health and Medical Education sought to launch a nationwide cohort study-the Prospective Epidemiological Research Studies in IrAN (PERSIAN)-in order to identify the most prevalent NCDs among Iranian ethnicities, and to investigate effective methods of prevention. The PERSIAN cohort consists of four population-based cohorts, the adult component, presented in this article, is a prospective cohort including 180,000 individuals aged 35-70 years, from 18 distinct areas of Iran. Upon joining, participants respond to interviewer-administered questionnaires. Blood, urine, hair and nail samples are collected and stored. To ensure consistency, centrally-purchased equipment is sent to all sites, and the same team trains all personnel. Routine visits and quality assurance/control measures are taken to ensure protocol adherence. Participants are followed for 15 years post-enrollment. The PERSIAN cohort is currently in the enrollment phase; cohort profiles will soon emerge.