The actual pathology of the Nicolau syndrome (NS) is still unknown. It is thought to involve direct vascular damage and vasospasm. Many NS cases were reported in the literature but a treatment protocol is still not established. However, after demarcation of the necrotic tissue, surgical intervention is mandatory. Five NS cases with extensive tissue necrosis on the upper lateral gluteal region were analyzed retrospectively. Operative technique was described in details for freestyle perforator-based fasciocutaneous flaps from the gluteal region to reconstruct defects of NS-related tissue necrosis. Freestyle perforator-based fasciocutaneous flaps were used for defect closure in all patients. All flaps survived totally. No complications occurred during the follow-up period. Although rare, NS is a serious complication of inadvertent intramuscular injections. Prevention is the best treatment. However, in case of large-tissue necrosis, freestyle perforator-based fasciocutaneous flaps harvested from the gluteal region is a satisfactory option for reconstruction.