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According to a Cochrane analysis (CD006544) prostanoids differ in their effects on rest-pain relief and ulcer healing. Objectives: To study the efficacy and safety of prostanoids for critical limb ischemia. Methods: Systematic literature search and meta-analysis (mixed treatment comparison) was performed. Results: Seven randomized controlled trials including 964 patients were analyzed. Compared to placebo, both alprostadil (OR: 3.2 95% CI: 1.7-5.5 and OR: 1.8 95% CI: 0.6-4.3) and iloprost (OR: 2.7 95% CI: 1.7-4.2 and OR: 2.5 95% CI: 1.0-5.4) were more efficacious with regard to rest-pain relief and ulcer healing and the difference between the two prostanoids was not significant (OR: 1.2 95% CI: 0.7-1.9 and OR: 0.74 95% CI: 0.3-1.5). Adverse events occurred significantly more often with both drugs compared to placebo, however, they were less frequent with alprostadil than with iloprost (OR 0.2 95% CI: 0.1-0.3). Conclusions: Prostanoids have favorable effect on rest-pain relief and ulcer healing in critical limb ischemia, without statistically significant difference between the two available drugs. 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