Background: Very few studies have examined the impacts of coal mine fire smoke on human health. The aim of this study was to assess the association between prolonged mine fire smoke PM2.5 exposure from a coal mine fire that burned over a six week period in 2014 and medications dispensed across five localities in South-eastern Victoria, Australia. Maximum hourly mine fire-related PM2.5 concentrations were estimated to reach 3700 μg/m3.Methods: Spatially resolved PM2.5 concentrations were retrospectively modelled using The Air Pollution Model, a dispersion model coupled with a chemical transport model (TAPM-CTM). Data on medications dispensed were collected from the Pharmaceutical Benefits Schedule database for 2013-2016. Poisson distributed lag time series analysis was used to examine associations between daily mine fire-related PM2.5 concentrations and daily counts of medications dispensed for respiratory, cardiovascular and mental health conditions. Confounding variables included: seasonality, long-term trend, day of the week, maximum ambient temperature and public holidays.Results: Positive associations were found between mine fire-related PM2.5 and increased risks of medications dispensed for respiratory, cardiovascular and mental health conditions, after lag 2-5 days. A 10 μg/m3 increase in coal mine fire-related PM2.5 was associated with a 15% (95%CI 8-23%) increase in respiratory medications dispensed, a 12% (9-16%) increase in cardiovascular medications dispensed and a 17% (12-22%) increase in mental health medications dispensed.Conclusions: Mine fire PM2.5 exposure was associated with increased medications dispensed for respiratory, cardiovascular and mental health. These findings can help to develop the public health response in the event of future mine fires.