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Purpose: Dexamethasone has been shown to prevent post-operative nausea and vomiting (PONV) and seems to reduce post-operative pain. Both factors, which can extend the hospital stay, delay rehabilitation, and impact patient satisfaction. Because of the immunosuppressive and glucose-rising effects of dexamethasone, there has been concern of its safety in arthroplasty surgery. The purpose of our study was to examine infection safety of dexamethasone in arthroplasty surgery with enough large study material to reliably detect a possible, even small, difference in infection incidence.Methods: A total of 18,872 consecutive primary and revision hip and knee arthroplasties were analyzed with data gathered from clinical information databases and a surgical site infection surveillance database with prospective data collection. Also, emergency operations due to fractures were included except for hip hemiarthroplasties.Results: During the follow-up, 189 (1.0%) prosthetic joint infections (PJIs) occurred: 0.8% after primary arthroplasty and 1.9% after revision arthroplasty. Dexamethasone was used in 2922 (15.5%) operations. The PJI rate in the dexamethasone group was 1.1% (31/2922) and in the non-dexamethasone group 1.0% (161/15950), with no significant difference in the risk of PJI between the two groups (OR 1.052, 95% CI 0.715-1.548, P = 0.773).Conclusions: In our study material, the use of a single 5-10 mg dose of dexamethasone did not increase the incidence of post-operative PJI. A low dose of dexamethasone may be safely used to prevent PONV and as part of multimodal analgesia on patients undergoing arthroplasty operation. [ABSTRACT FROM AUTHOR]