Preterm birth causes an increased risk for perinatal morbidity and mortality.To determine whether mid-trimester 17-alpha-hydroxyprogesterone caproate (17-OHPC) reduces the risk of recurrent preterm birth and adverse perinatal outcomes.Systematic search to identify relevant studies published in different languages, registered after 2000, using appropriate MeSH terms.Inclusion criteria were women between 16 and 26 weeks of pregnancy with history of preterm delivery in any pregnancy randomized to either 17-OHPC or placebo/no treatment.The number of preterm births and adverse outcomes in the 17-OHPC and placebo arms over the total number of patients in each randomized group were used to calculate the risk ratio (RR) by random-effects models using the Mantel-Haenszel method. Between-study heterogeneity was assessed using tau , χ (Cochrane Q), and I statistics.Four studies were included. There was a 29% (RR 0.71; 95% CI, 0.53-0.96; P=0.001), 26% (RR 0.74; 95% CI, 0.58-0.96; P=0.021), and 40% (RR 0.60; 95% CI, 0.42-0.85; P=0.004) reduction in recurrent preterm birth at <37, <35, and <32 weeks, respectively, in the 17-OHPC group compared with placebo. The reduction in neonatal death was 68% (RR 0.32; 95% CI, 0.15-0.66; P=0.002).17-OHPC could reduce the risk of recurrent preterm birth at <37, <35, and <28 weeks and neonatal death.CDR42017082190.