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During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period.We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2−+NO3−, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2−+NO3−) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index).Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): −15.3 (5.8–24.8), P = .002; −20.0 (5.5–34.5), P = .008; and −10.4 (2.5–18.3), P = .011, respectively. In the RIPC group, EBC NO2−+NO3− and H2O2 levels were also lower than in controls at T2 and T1–T3, respectively (all P < .05). Blood levels of 8-isoprostane and NO2−+NO3− were lower in the RIPC group at T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2 hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for differences between means: 78 (10–146), 66 (14–118), and 58 (12–104), respectively.Limb RIPC decreased EBC 8-isoprostane levels and other oxidative lung injury markers during lung lobectomy. RIPC also improved postoperative gas exchange as measured by PaO2/FiO2 ratio.