Background : The efficacy of corticosteroids for patients with septic shock remains controversial. Therefore, evaluating a specific corticosteroid treatment could solve the conflicting results of past studies. We performed this systematic review and meta-analysis to elucidate the beneficial effects of a dual corticosteroid treatment regime involving administration of both hydrocortisone and fludrocortisone for adult patients with septic shock on mortality.Methods : We searched the Medline, Cochrane CENTRAL, and ICHUSHI databases from inception to April 2019. We included peer-reviewed randomized controlled trials that compared the use of both hydrocortisone and fludrocortisone with either corticosteroid-free or hydrocortisone-only treatments on adult patients with septic shock. Three researchers independently reviewed the studies for design, eligibility criteria of patients, dose of each corticosteroid, and duration of corticosteroid therapy following PRISMA guidelines. The random-effects models and Grading of Recommendations Assessment, Development and Evaluation were applied to rate the quality of the evidence. Primary outcome was 28-day mortality, and secondary outcomes were in-hospital mortality, long-term mortality, shock reversal, and adverse events. Results : Among the four studies eligible for data synthesis, we included 2050 patients from three studies for quantitative synthesis. All studies used similar regimens (50 mg intravenous bolus of hydrocortisone every 6 h and 50 μg tablets of fludrocortisone once daily for 7 days without tapering). The 28-day mortality rate was reduced after dual corticosteroid treatment [risk ratio, 0.88; 95% confidence intervals (CI), 0.78–0.99]. The heterogeneity between the studies was low (I² = 0%). Furthermore, the certainty in the effect estimates was high. Patients that underwent dual corticosteroid treatment had lower long-term mortality rates (RR, 0.90, 95% CI, 0.83–0.98) and higher rate of shock reversal after 28 days (odds ratio, 1.06; 95% CI, 1.01–1.12) than control patients. Adverse events (except for hyperglycemia) were similar among the treatment groups.Conclusions : The available evidence suggests that a combination of fludrocortisone and hydrocortisone is more effective than adjunctive therapy and may be recommended for patients with septic shock.