BACKGROUND: Cardiopulmonary bypass and cardiac surgery are associated with a significant systemic inflammatory response that may increase postoperative complications. This meta-analysis assessed whether the benefits and risks of corticosteroid use were dose dependent in adult cardiac surgery. METHODS AND RESULTS: Randomized controlled trials of the use of corticosteroid prophylaxis in adult cardiac surgery (>18 years of age) requiring cardiopulmonary bypass were selected from MEDLINE (1966 to August 1, 2008), EMBASE (1988 to August 1, 2008), and the Cochrane controlled trials register without any language restrictions. A total of 3323 patients from 50 randomized controlled trials were identified and subject to meta-analysis. Corticosteroid prophylaxis reduced the risk of atrial fibrillation (25.1% versus 35.1%; number needed to treat, 10; relative risk, 0.74; 95% confidence interval [CI], 0.63 to 0.86; P<0.01) and length of stay in the intensive care unit (weighted mean difference, -0.37 days; 95% CI, -0.21 to -0.52; P<0.01) and hospital (weighted mean difference, -0.66 days; 95% CI, -0.77 to -1.25; P=0.03) compared with placebo. The use of corticosteroid was not associated with an increased risk of all-cause infection (relative risk, 0.93; 95% CI, 0.61 to 1.41; P=0.73), but hyperglycemia requiring insulin infusion after corticosteroid prophylaxis was common (28.2%; relative risk, 1.49; 95% CI, 1.11 to 2.01; P<0.01). No additional benefits were found on all outcomes beyond a total dose of 1000 mg hydrocortisone, and very high doses of corticosteroid were associated with prolonged mechanical ventilation. CONCLUSIONS: Evidence suggests that low-dose corticosteroid is as effective as high-dose corticosteroid in reducing the risk of atrial fibrillation and duration of mechanical ventilation but with fewer potential side effects in adult cardiac surgery.