This study was planned to compare the computed tomographic detectability of lung nodules in three ventilatory conditions: total lung capacity, high-frequency ventilation, and total lung deflation. In an ex vivo lung model, 44 nodules were simulated. Using computed tomography (CT) scans, nodules were detected and compared to the actual number and excised under CT guidance. Simulated nodules measured 6.2 +/- 2.1 mm and demonstrated an attenuation of 175 +/- 14 HU. Observer confidence was highest at total lung capacity (5.00 +/- 0.00), in comparison to high-frequency ventilation and total lung deflation (4.69 +/- 0.78, 4.94 +/- 0.27, p = .24). The kappa score for total lung capacity, high-frequency ventilation, and total lung deflation was 1.00, 0.96, and 0.98, respectively, indicating a very high interrater reliability. Although surgical devices generated a substantial artifact, 90% of nodules were excised. Thus, although total lung capacity produces the highest confidence level, all three of the ventilatory techniques examined have similar detection of subcentimeter pulmonary nodules using computed tomography scans.