Abstract: Objective To observe the clinical effects of sequential treatment with extensive lesion resection, vacuum sealing drainage (VSD) combined with irrigation of oxygen-loaded fluid, and tissue transplantation on hidradenitis suppurativa (HS) in buttocks which recurred after multiple surgeries. Methods From January 2012 to March 2017, 15 male patients (aged 26-53 years) hospitalized in our burn ward with Hurley′s stage Ⅲ HS in the buttocks recurred after 2-5 operations who met the inclusion criteria were enrolled in the prospective self pre- and post-control study. After extensive resection of the lesion, continuous VSD combined with intermittent irrigation of oxygen-loaded fluid was given, with negative pressure of -16.7 kPa and flow rate of pure oxygen of 1.0 L/min. After 7 days of treatment with VSD combined with irrigation of oxygen-loaded fluid, the negative pressure device was removed and autologous posterior thigh split-thickness skin grafts and/or local flaps were transplanted to repair the wounds. Six patients were performed with split-thickness skin grafting, 4 patients with local flap transplantation, and 5 patients with split-thickness skin grafting together with local flap transplantation. The donor sites of local flaps were sutured directly or transplanted with autologous posterior thigh split-thickness skin grafts, and the donor sites of split-thickness skin grafts with autologous thin split-thickness scalp. The wound tissue or wound granulation tissue was collected before lesion resection and 7 days after treatment with VSD combined with irrigation of oxygen-loaded fluid respectively for bacterial culture and detecting of the content of tumor necrosis factor-alpha (TNF-α) by enzyme-linked immunosorbent assay. Survival of skin grafts and flaps after operation was observed, hospitalization time was recorded, and recurrence and complications of HS were followed up. Data were processed with paired sample t test. Results Bacterial culture result of wound tissue before lesion resection was positive in all patients, mainly Staphylococcus, Streptococcus, Proteus mirabilis, and anaerobic bacteria, etc., while that of wound granulation tissue after 7 days of treatment with VSD combined with irrigation of oxygen-loaded fluid was negative. The content of TNF-α in wound granulation tissue after 7 days of treatment with VSD combined with irrigation of oxygen-loaded fluid was (10.1±2.9) pg/L, significantly lower than (73.6±5.6) pg/L before lesion resection (t=33.47, P<0.01). The skin grafts and/or flaps of 15 patients survived post operation, and the wounds were healed. The patients were hospitalized for 17-31 days. During follow-up of 1 to 5 years, no recurrence of HS occurred in operative site of buttocks of 15 patients, but 1 patient had ulceration of healed perianal incision caused by high anal fistula and was healed after treatment. Conclusions Sequential treatment with extensive resection, VSD combined with irrigation of oxygen-loaded fluid, and tissue transplantation can thoroughly remove HS lesions in the buttocks and improve the condition of wound bed for skin acceptance after debridement, which is conducive to the cure of HS in the buttocks which has undergone multiple operations but still recurs after operation.