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Clinical relevanceScientific rationale for study: Many methods have been tried to 'smooth' post-operative period after surgical extraction of impacted third molars, including pharmacological means. Local application of dexamethasone seems to be a simple and effective way. Quality of life measures have recently been included in assessment of surgical outcomes. Principal findings: Clinically significant effects of local and systemic steroid on post-operative sequelae as compared to control. Practical implications: Providing good post-operative course after oral surgery by simple and available method. AbstractAim: The aim of this randomised non-blind prospective study was to compare the effect of dexamethasone sodium phosphate 4 mg in five different routes of administration on post-operative sequelae and quality of life (QOL) measures for patients undergoing surgical removal of impacted lower third molars. Material and methods: A total of 72 patients (32 males and 40 females) were included in the study and were randomly divided into six equal study groups: five treatment groups received dexamethasone 4 mg as intramuscular injection, intravenous injection, oral tablets, submucosal injection and endoalveolar powder; and control group which received no dexamethasone. Swelling, trismus and pain were evaluated at the first, third and seventh day post-operatively. A modified questionnaire was used to measure different aspects of QOL. Results: All dexamethasone groups showed statistically significant improvement in swelling and pain at all intervals (P < 0.05) and in trismus at day 1 and day 3 intervals (P < 0.05) as compared to control. QOL measures also showed significant improvement (P < 0.01). Results among treatment groups were comparable for all parameters. No relevant side effects were seen nor reported. Conclusions: Local routes of dexamethasone administration showed comparable effect to systemic routes and were simple, safe, painless and costeffective therapeutic options.