182 patients scheduled for total knee arthroplasty were randomized to either perioperative intravenous dexamethasone administration, including one dose preoperative and subsequent doses at 24 and 48 hours afterward, to a single preoperative intravenous dexamethasone infusion, or to no dexamethasone administration. Patients were assessed for pain scores, analgesic consumption, incidence of postoperative nausea and vomiting, antiemetic use, and the incidence of complications. Results demonstrated that the use perioperative intravenous dexamethasone was associated with lower pain scores and requirement of oral oxycodone compared to both a single, preoperative intravenous dose of dexamethasone and compared to no dexamethasone, as well as demonstrated a significant reduction in the incidence of PONV and requirement of rescue metoclopramide compared to no dexamethasone.