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Experimental and clinical trials demonstrate the vascular, anti-ischemic and tissue protective effects of PGE1, which has been used for many years in different macrovascular diseases. However, few reports have addressed its potential use in microvascular surgery. The authors share their early experience with PGE1 in replantations and free tissue transfers. Considering its established benefits and minimal adverse reactions, PGE1 might be included as a first-line medication in the antithrombotic pharmacologic treatment in replantation and free flap surgery. However, the overall clinical efficacy and safety of PGE1 in microvascular surgery remains to be determined in larger, prospective clinical trials.