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Vacuum-assisted closure (vacuum sealing) is a surgical procedure for the local treatment of severe soft-tissue damage. However, systemic consequences to the host are unknown. The aim of this study was to disclose the effects of vacuum sealing on the host’s immune response and to demonstrate the early time course of endotoxin, interleukin-6 (IL-6), C-reactive protein (CRP), haptoglobin, transferrin, orosomucoid, 6-keto-prostaglandin (6KPG), α1-antitrypsin and complement C3 and C4. A total of 35 patients with closed ankle fractures were randomized into two groups and operated on within 6 h after injury. After osteosynthesis, one group was treated by vacuum sealing (VS) and the other by immediate skin closure (IS). Blood was collected immediately after admission and regularly up to 96 h after surgery. Morbidity was checked during the first year after injury. Preoperative endotoxin plasma level was increased compared with that of voluntary individuals (0.06 ± 0.02 EU/ml versus 0.021 ± 0.001 EU/ml) and peaked in patients with immediate skin suture 0.5 h after the surgical procedure at 0.11 ± 0.03 EU/ml. However, in patients with vacuum sealing, this peak was absent (0.07 ± 0.02 EU/ml). Endotoxaemia decreased to almost normal values after 24 h. Plasma IL-6 peaked 12 h postoperatively, decreasing thereafter with no difference between the groups. The plasma level of 6KPG decreased immediately after the surgical procedure in vacuum-sealed patients (before operation, 415 pg/ml; 12 h later, 251 pg/ml), but increased first in patients with immediate skin suture. CRP peaked 48 h after injury (VS, 48 ± 6 mg/l; IS, 38 ± 7 mg/l) with no difference between the groups. Transferrin decreased postoperatively (pre-op: VS, 2.49 ± 0.14 g/l; IS, 2.85 ± 0.19 g/l; 24 h: VS, 2.16 ± 0.08 g/l and IS 2.33 ± 0.11 g/l), whereas haptoglobin (pre-op: VS, 2 ± 0.21 g/l; IS, 1.7 ± 0.18 g/l; 96 h: VS, 3.4 ± 0.25... [ABSTRACT FROM AUTHOR]