BACKGROUND Tehran, the 22nd most populous city in the world, has the highest mortality rate due to respiratory system diseases (RSDs) in Iran. This study aimed to investigate spatiotemporal patterns of mortality due to these diseases in Tehran between 2008 and 2018. METHODS We used a dataset available from Tehran Municipality including all cases deceased due RSDs in this city between 2008 and 2018. Global Moran's I was performed to test whether the age-adjusted mortality rates were randomly distributed or had a spatial pattern. Furthermore, Anselin Local Moran's I was conducted to identify potential clusters and outliers. RESULTS During the 10-year study, 519,312 people died in Tehran, 43,177 because of RSDs, which corresponds to 831.1 per 10,000 deaths and 5.0 per 10,000 population. The death rate was much higher in men (56.8%) than in women (43.2%) and the highest occurred in the > 65 age group (71.2%). Overall, three diseases dominated the mortality data: respiratory failure (44.2%), pneumonia (15.9%) and lung cancer (10.2%). The rates were significantly higher in the central and southeastern parts of the city and lower in the western areas. It increased during the period 2008-2018 and showed a clustered spatial pattern between 2008 and 2013 but presented a random geographical pattern afterwards. CONCLUSIONS This study provides a first report of the spatial distribution of mortality due to RSDs in Tehran and shows a significant increase in respiratory disease mortality in the last ten years. Effective control of the excess fatality rates would warrant a combination of urban prevention and treatment strategies including environmental health plans.