The effect of endo-alveolar and sub-mucosal administration of dexamethasone sodium phosphate to prevent inflammatory sequelae after surgical removal of lower third molars was studied. Forty-three patients underwent bilateral extractions of lower third molars and were randomly assigned to receive either dexamethasone 4 mg (group A) or 10 mg (group B) as endo-alveolar powder or 10 mg as sub-mucosal injection (group C) unilaterally. The controlateral site served as control and did not receive any steroid administration. Facial edema, trismus and pain perception were evaluated at the 2nd and 7th postoperative day. A multivariate analysis revealed that treatment and ostectomy time were both significantly positively associated with the degree of postoperative trismus and edema. Other baseline classification variables (e.g., molar classification) were also predictive of the degree of change in all clinical parameters. Test sites treated (any steroid application) showed greater reductions in all clinical parameters recorded compared to control. No statistically significant differences were observed between the three test groups. Both sub-mucosal and endo-alveolar administration of dexamethasone are effective in reducing postoperative sequelae of surgical removal of lower wisdom teeth.