BACKGROUND/AIM The protective effects of prostaglandin (PG) analogs on ischemia-reperfusion (I/R) have been well documented; however, comparative studies are lacking. The aim of the present study was to determine whether iloprost or alprostadil is more effective in preventing muscle I/R injury. MATERIALS AND METHODS Thirty-two rats were divided into four groups (n = 8): sham, control, IL (I/R + iloprost), and AL (I/R + alprostadil). I/R was induced by a tourniquet in the hindlimb for 3 h/3 h. The IL and AL groups received iloprost (0.5 ng kg-1 min-1) and alprostadil (0.05 µg kg-1 min-1) during reperfusion, respectively. After 6 h, blood and muscles were collected for analyses. RESULTS Serum TNF-α and IL-1β levels were decreased in the IL and AL groups compared with the control group (P < 0.05), whereas IL-6 levels did not change significantly. Tissue malondialdehyde levels were significantly lower in the IL and AL groups (P < 0.05). Tissue catalase levels showed no difference. The histological damage scores and apoptosis scores were both significantly decreased in the IL and AL groups compared with the control group (P< 0.05). CONCLUSION The present study indicated that iloprost and alprostadil attenuated I/R injury in skeletal muscle. However, no comparable difference was evident regarding the efficacies of either PG analog.