Background: Resection of lung cancer infiltrating the aortic arch or the subclavian artery can be accomplished in selected patients with the use of cardiopulmonary bypass (CPB). Direct cross-clamping of the aortic arch and the left subclavian artery without CPB for radical resection of the tumor can be an alternative. This study presents one group's experience with this technique. Methods: Between October 2016 and May 2019, 9 patients (5 male, 4 female) underwent radical resection of lung cancer infiltrating the aortic arch (n = 5) or the left subclavian artery (n = 4) by direct cross-clamping technique at Sapienza University of Rome, Italy. Seven left upper lobectomies, 1 left pneumonectomy, and 1 left upper sleeve lobectomy were performed. Reconstruction of the aortic arch was performed by direct suturing or polyethylene terephthalate (Dacron) patch, whereas the subclavian artery was reconstructed with a Dacron conduit. Three patients received neoadjuvant chemotherapy. Results: Patients’ mean age was 64.7 ± 13.3 years (range, 36 to 78 years). Aortic arch resection was partial in all cases (adventitial in 1 and full thickness in 4); left subclavian artery resection was adventitial in 2 patients and circumferential in 2. All the resections were complete. Prosthetic reconstruction was performed in 4 cases. Mean operative time was 130 ± 25.6 minutes; mean vascular clamping time was 28.2 ± 3.2 minutes. No mortality occurred. The major complication rate was 11.1 %. At a mean follow-up of 17 ± 9 months (range, 5 to 29 months), the recurrence rate was 33.3%. Median survival was 20 months. Conclusions: Direct cross-clamping as an alternative to CPB for resection of lung cancer infiltrating the aortic arch or the subclavian artery is a feasible, safe, and reliable procedure in selected patients.