question: Disease registry systems provide a strong information infrastructure for decision-making and research. The purpose of this study is to describe the implementation method and protocol of the COVID-19 registry in Khuzestan province, Iran. We established a steering committee and formulated the purposes of the registry. Then, based on reviewing the literature, and expert panels, the minimum data set, the data collection forms and the web-based software were developed. Data collection is done retrospectively through Hospital Information Systems, Medical Care Monitoring Center system (MCMC), Management of Communicable Disease Prevention and Control system (MCDPC) as well as, patients' records. For prospective data collection, the data collection forms are compiled with patients' medical records by the medical staff and are then entered into the registry system. We collect patients' administrative and demographic data, history and physical examinations, test and imaging results, disease progression, treatment, outcomes, and follow-ups of the confirmed and suspected inpatients and outpatients. From April 20 to December 5, 2020, the data of 4,812 confirmed cases and 7,113 suspected cases were collected from two COVID-19 referral hospitals. Based on our experience, recording information along with providing care for patients and putting patients' data registration in the medical staff's routine, structuring data, having a flexible technical team and rapid software development for multiple and continuous updates, automating data collection by connecting the registry to existing information systems and having different incentives, the registration process can be strengthened.