We performed thoracoscopic surgery for pneumothorax using two-lung ventilation with low tidal volume and evaluated the feasibility and safety of this procedure. Forty-six patients (mean age, 23.6 +/- 10.47 years) each with a primary spontaneous pneumothorax underwent wedge resection with chemical and mechanical pleurodesis. Two-lung ventilation anesthesia was performed with a single-lumen endotracheal tube, and the tidal volume was reduced to 4 mL/kg; the respiratory rate was increased to 24 cycles/min. Airway pressure, end-tidal CO(2), and the results of blood gas analysis were obtained right after endotracheal intubation and during the operation, and were compared. The tidal volume was 496.2 +/- 94.33 mL at anesthesia induction, which decreased to 243.9 +/- 34.43 mL during the two-lung ventilation. In 5 patients, the tidal volume was additionally decreased by 32.5 +/- 12.58 mL (p = 0.014) to obtain an optimal working field. The differences between the airway pressure, pH, partial pressure of carbon dioxide, and partial pressure of oxygen were significant between the two measurement times. However, all of the values of the arterial blood gas analysis were within normal range. The oxygen saturation (99.9% +/- 0.69% versus 99.8 +/- 0.72%; p = 0.160) and end-tidal CO(2) (33.2 +/- 3.74 mm Hg versus 34.1 +/- 4.19 mm Hg; p = 0.157) were not significantly different. The time from intubation before the incision was 17.1 +/- 4.18 minutes, the operation time was 31.9 +/- 14.48 minutes, and the total anesthesia time was 65.8 +/- 15.02 minutes. Thoracoscopic surgery for primary spontaneous pneumothorax using two-lung ventilation with low tidal volume was technically feasible.