OBJECTIVES: Maintenance oral corticosteroids (mOCS) are used in the treatment of severe asthma where patients have exhausted other available options without achieving acceptable control of their symptoms. However, long-term mOCS is associated with the development of a number of serious adverse events. These complications cause considerable healthcare costs and quality-adjusted life year (QALY) losses. The aim of this study was to establish the excess risk of complications associated with long-term mOCS use, and to quantify the cost and QALY burden of these events. METHODS: A systematic review was undertaken to identify any studies reporting adverse event risk due to mOCS treatment. Seventy-two (72) studies were identified. The review focussed on eight disease outcomes representing the bulk of the mOCS cost and QALY burden: type II diabetes, myocardial infarction, glaucoma, cataract, ulcer, osteoporosis, infection, and stroke. A risk estimate for each adverse event was selected, based on the daily dose and mOCS exposure that best represented asthma-related mOCS use in Australian clinical practice. The excess risk of each complication in patients receiving mOCS, relative to those patients not receiving mOCS, was applied to the annual cost and QALY burden of each event in the Australian population. The cost and QALY burden attributable to mOCS was estimated on a per patient per year basis.  RESULTS: The expected annual cost of mOCS-related disease outcomes was estimated to be $598.32 per patient per year. Each patient treated with mOCS also suffers a QALY loss of 0.0367 per year of treatment. These effects are considered reversible once patients stop taking mOCS. CONCLUSIONS: mOCS are associated with a clear cost and QALY burden for patients with severe asthma which is likely underestimated by the approach adopted in this study. These results are likely to be useful for economic evaluations of new asthma interventions which replace or delay mOCS.