PURPOSE: We aimed to describe our initial experience with percutaneous transthoracic localization (PTL) of pulmonary nodules using a C-arm cone-beam CT (CBCT) virtual navigation guidance system. METHODS: From February 2013 to March 2014, 79 consecutive patients (mean age, 61±10 years) with 81 solid or ground-glass nodules (mean size, 12.36±7.21 mm; range, 4.8-25 mm) underwent PTLs prior to video-assisted thoracoscopic surgery (VATS) excision under CBCT virtual navigation guidance using lipiodol (mean volume, 0.18±0.04 mL). Their procedural details, radiation dose, and complication rates were described. RESULTS: All 81 target nodules were successfully localized within 10 mm (mean distance, 2.54±3.24 mm) from the lipiodol markings. Mean number of CT acquisitions was 3.2±0.7, total procedure time was 14.6±5.14 min, and estimated radiation exposure during the localization was 5.21±2.51 mSv. Postprocedural complications occurred in 14 cases (17.3%); complications were minimal pneumothorax (n=10, 12.3%), parenchymal hemorrhage (n=3, 3.7%), and a small amount of hemoptysis (n=1, 1.2%). All target nodules were completely resected; pathologic diagnosis included invasive adenocarcinoma (n=53), adenocarcinoma-in-situ (n=10), atypical adenomatous hyperplasia (n=4), metastasis (n=7), and benign lesions (n=7). CONCLUSION: PTL procedures can be performed safely and accurately under the guidance of a CBCT virtual navigation system.