BackgroundRheumatic heart disease (RHD) remains a disease of international importance, yet little has been published about disease progression in a contemporary patient cohort. Multi‐state models provide a well‐established method of estimating rates of transition between disease states, and can be used to evaluate the cost‐effectiveness of potential interventions. We aimed to create a multi‐state model for RHD progression using serial clinical data from a cohort of Australian patients.Methods and ResultsThe Northern Territory RHD register was used to identify all Indigenous residents diagnosed with RHD between the ages of 5 and 24 years in the time period 1999–2012. Disease severity over time, surgeries, and deaths were evaluated for 591 patients. Of 96 (16.2%) patients with severe RHD at diagnosis, 50% had proceeded to valve surgery by 2 years, and 10% were dead within 6 years. Of those diagnosed with moderate RHD, there was a similar chance of disease regression or progression over time. Patients with mild RHD at diagnosis were the most stable, with 64% remaining mild after 10 years; however, 11.4% progressed to severe RHD and half of these required surgery.ConclusionsThe prognosis of young Indigenous Australians diagnosed with severe RHD is bleak; interventions must focus on earlier detection and treatment if the observed natural history is to be improved. This multi‐state model can be used to predict the effect of different interventions on disease progression and the associated costs.