A systematic review of the literature identified nine randomised trials that evaluated the effects of progestational agents in the prevention of preterm delivery. These studies were of variable quality. Meta-analyses showed reductions in delivery rates before 37 weeks (OR 0.42, 95% CI 0.31-0.57) and 34 weeks (OR 0.51, 95% CI 0.34-0.77) as well as in respiratory distress syndrome (OR 0.55, 95% CI 0.31-0.96) with progestational agents. A cumulative meta-analysis showed that the treatment benefit for the outcome of delivery before 37 weeks exceeded the conventional level of statistical significance in 1975 (p<0.01); by 1985, the p-value was <0.001, and by 2003, it was <0.0001. Another cumulative meta-analysis in which the studies were added to the pooled analysis by decreasing quality score showed significant benefit even when the analysis was limited to just the highest quality trials (OR 0.47, 95% CI 0.33, 0.66, p<0.0001). An exploration of the applicability of the effects across various baseline risks using a L'abbe plot found that the benefit was consistent across a range of risks. A comprehensive review of both trial and observational data on harm did not show any demonstrable evidence of harm to mother and baby. Women at high risk of preterm birth should be recommended progestational agent therapy.