Purpose The aim of this study was to demonstrate the effectiveness of prophylactic dexamethasone and compare the different routes of administration for the control of pain, edema, and trismus after surgery on the wisdom teeth, taking into consideration the general preference for the oral route over the intramuscular route. Therefore, it is hoped that the results of this work will allow us to determine the most effective dose and route and contribute to the generation of guidelines to improve the postoperative management of our patients. Methods The study included a total of 52 patients, of which 38 were females and 14 were males (age range 18–25 years; X = 21.60; Σ = 2.24); 26 received dexamethasone intramuscularly and 26 orally. Five patients were excluded for not complying with postoperative instructions. Results At the postoperative control, there were no differences between the parenteral and oral pathways in the control of facial edema and trismus for the periods evaluated. Patients in both groups presented with postoperative pain; and no differences were found for all of the periods evaluated, with the exception of 48 hours, in which case, 8 mg dexamethasone was used. The parenteral route was more effective (P = .000). At the postoperative control, as shown in Table IV, administration of dexamethasone via the parenteral route showed changes in edema and trismus compared with the preoperative evaluation (edema P = .000 and trismus P = .000); with regard to pain, no changes were reported at 24 hours (P = 1.000) or at 48 hours (P = .327). However, oral dexamethasone, as shown in Table V, changes in edema (P = .000), trismus (P = .000), and pain at 24 and 48 hours (P = .000) were noted; with regard to immediate postoperative pain, no changes were observed (P = .327). Table IV . Efficacy of parenteral dexamethasone prophylaxis to control edema, trismus and postoperative pain after surgery of wisdom teeth. Table V . Efficacy of oral dexamethasone prophylaxis to control edema, trismus and postoperative pain after surgery of wisdom teeth. Conclusions Intramuscular administration of dexamethasone showed no difference in effectiveness compared with the oral route with regard to edema, pain, and trismus after wisdom tooth surgery, except for the 48-hour period, during which intramuscular dexamethasone was more effective. Intermuscular dexamethasone route was effective to control pain at 24 and 48 hours after wisdom tooth surgery. Oral dexamethasone was effective in controlling pain immediately after wisdom tooth surgery.