Background. A Cochrane review in 2006 concluded that further knowledge is required before recommendation can be made with regard to progesterone in the prevention of preterm birth. Objective. To provide an update on the preventive effect of progesterone on preterm birth in singleton pregnancies. Search strategy. A search in the PubMed, Embase, and Cochrane database was performed using the keywords: pregnancy, progesterone, preterm birth/preterm delivery, preterm labor, controlled trial, and randomized controlled trial. Selection criteria. Studies on singleton pregnancies. Data collection and analysis. A meta-analysis was performed on randomized trials including singleton pregnancies with previous preterm birth. Main results. Two new randomized controlled trials of women with previous preterm birth were added to the four analyzed in the Cochrane review, and the meta-analysis of all six studies now showed that progesterone supplementation was associated with a significant reduction of delivery before 32 weeks and of perinatal mortality. Furthermore, a third trial showed a positive effect on women with a short cervix at 23 weeks, and a fourth study showed that progesterone reduces the risk of preterm delivery in women with preterm labor. Conclusions. In women with a singleton pregnancy and previous preterm delivery, progesterone reduces the rates of preterm delivery before 32 weeks, perinatal death, as well as respiratory distress syndrome and necrotizing enterocolitis in the newborn. Women with a short cervix or preterm labor may also benefit from progesterone, but further evidence is needed to support such a recommendation. Follow-up studies should focus on possible metabolic complications in the mother or the offspring.