A meta-analysis included eight studies (5 RCTs and 3 N-RCTs) of hydrocortisone (HC) combined with fludrocortisone (FC) in septic shock in adults. Compared with placebo (from an RCT), the combination significantly reduced 28-day mortality (RR 0.84; 95% CI 0.76-0.94; p=0.002), 90-day mortality (RR 0.82; 95% CI 0.71-0.94; p=0.006) and in-hospital mortality (RR 0.85; 95% CI 0.71-0.94; p=0.006). CI 0.77-0.94; p=0.002). No significant survival advantage over HC alone was observed in either RCT (n=553) or N-RCT (n=88,666; 28-day mortality RR 0.99; p=0.79). The combination of HC + FC was associated with a higher reinfection rate versus placebo (RR 1.13; p=0.03), but not versus HC alone (p=0.19). There was no increase in gastrointestinal bleeding or reduction in ICU/hospital stay. Evidence from RCTs suggests improved survival over placebo, but observational data do not demonstrate a benefit over HC.