Controlling postoperative pain and nausea after total joint arthroplasty remains an important challenge. We conducted a prospective, randomized controlled trial with 120 patients to determine if the addition of perioperative dexamethasone to a multimodal regimen improves antiemetic and analgesic control, enhances mobility, and shortens hospital length of stay after total hip and knee arthroplasty. Patients administered 10 mg of intravenous dexamethasone intraoperatively consumed less daily rescue anti-emetic and analgesic medication, reported superior VAS nausea and pain scores, ambulated further distances, and had a significantly shorter length of stay compared to the control group (p < 0.05). A second, 24-hour postoperative dose of 10 mg intravenous dexamethasone provided significant additional pain and nausea control and further reduced length of stay (p < 0.05). No adverse events were detected with the administration of the intraoperative and/or postoperative dexamethasone.