Nausea and vomiting are common complications of anaesthesia. Dexamethasone is an effective prophylaxis but is immunosuppressive and may increase postoperative infection risk. This retrospective cohort study examined the association between the administration of a single intraoperative anti-emetic dose of dexamethasone (4 to 8 mg) and postoperative infection in 439 patients undergoing single procedure, non-emergency surgery in a university trauma centre. Exclusion criteria included comorbidities, immunosuppressive medications or procedures that confer an increased infection risk. In the 10-week study period and three-month follow-up period, there were 98 documented infections (22.3% of the cohort), of which 43 were detected only on post-discharge follow-up. Anti-emetic dexamethasone was given to 108 patients (24.6%). Stepwise, multivariate logistic regression modelling identified significant associations between female gender, symptomatic reflux, respiratory disease and the risk of infection. The adjusted odds ratio for dexamethasone was 0.88 (0.5 to 1.5, P = 0.656). We did not demonstrate an association between anti-emetic doses of dexamethasone and postoperative infection.