Background: Antenatal glucocorticoid (AGC) therapy has been associated with a decrease in respiratory distress syndrome (RDS). While preterm males remain at greater risk of RDS than females, the role of fetal sex in AGC response is not well known. Objectives: To review the available evidence regarding the effect of fetal sex in the prevention of RDS using AGC. Method: We conducted a systematic review and meta-analysis of RCTs to compare the effect of AGC in male and female infants with regard to the rates of RDS, intra-ventricular hemorrhage (IVH) grades III and IV, and neonatal mortality. Random effects with 95% confidence intervals were assessed in both groups and relative risks were compared using mixed regression. Results: From 248 potentially eligible articles, we included eight in the analysis for a total of 1109 male and 968 female infants. Both male and female infants had a significant decrease in the risks, but no difference between the sexes was observed in terms of reduction in RDS (RR 0.50; 95% CI 0.33 to 0.77 for males, and RR 0.57; 95% CI 0.43 to 0.75 for females, P = 0.99), reduction in IVH (P = 0.98), and reduction in neonatal mortality (P = 0.43). In a sub-analysis, use of betamethasone was associated with a significant decrease in the rate of RDS in males (RR 0.29; 95% CI 0.15 to 0.57) but dexamethasone was not (RR 0.78; 95% CI 0.57 to 1.07). Conversely, dexamethasone use was significantly helpful in females (RR 0.51; 95% CI 0.32 to 0.81) but betamethasone was not (RR 0.62; 95% CI 0.38 to 1.00). Conclusion: The effect of AGC for prevention of RDS is similar in females and males. However, futures studies should investigate the type of AGC according to fetal/neonatal sex. © 2011 Society of Obstetricians and Gynaecologists of Canada.