Preterm labor is defined as birth before 37th week of pregnancy. Despite of progressive improvement in gynecological care, the prevalence of preterm labor is growing. The aim of this study was to investigate the effect of 17α-Hydroxyprogestrone Caproate on prevention of preterm labor in high-risk pregnant women. This doubleblinded clinical trial study was conducted on 100 pregnant women who admitted to Besat hospital, Sananadj, Iran during 2013-2014. Women were block randomized and divided in two intervention (n=50) and control (n=50) groups. The intervention group was injected 250 mg 17α-Hydroxyprogestrone Caproate intramuscularly during 24th until 34th week on a weekly basis and placebo was given to control group. The results showed that 11 women (22%) with preterm labor on less than 37 week and 39 (78%) on more than 37 week, however, in placebo group these figures were 29 (58%) and 21 (42%), respectively. This finding showed that 17α-Hydroxyprogestrone Caproate had preventive effect on preterm labor in intervention group. The logistic regression also showed that there was a significant difference between two intervention and control groups (p=0.001). It seems that 17α- Hydroxyprogestrone Caproate had preventive effect on preterm labor.