Background: Video-assisted thoracic surgery (VATS) lobectomy has been proved to have shorter hospital stay, less perioperative complications and less pain compared with lobectomy by thoracotomy, but severe intraoperative complications during VATS lobectomy is rare reported. We compared intraoperative safety between VATS lobectomy and lobectomy by thoracotomy. Methods: 659 patients with postoperative stage I and IIa non-small cell lung cancer (NSCLC) who underwent lobectomy in China-Japan Friendship Hospital from February 2008 to June 2012 were analyzed retrospectively, in which 277 were performed by thoracotomy, 357 performed by VATS, and 25 performed by VATS converted to open. Outcomes were analyzed to compare the incidence of significant bleeding, with conversion cases were included into VATS group. Results: Ten severe intraoperative complications were identified in 10 patients (6 in VATS, 4 in open), with no intraoperative deaths. The incidence of severe intraoperative complications was similar between VATS group and thoracotomy group [1.57% (6/382) vs. 1.44% (4/277), P=1.0]. Most severe intraoperative complications were related to the injury of major pulmonary vessels (9/10), and most of these complications occurred during upper lobectomy (8/10). There was no statistically significant difference in blood loss (242.85+/-220.47 vs. 240.43+/-144.36, P=0.865), and operative time (198.00+/-75.24 vs. 208.05+/-61.97, P=0.061) between the open and VATS groups, respectively, but blood loss and operative time are significant different after elimination of conversion cases (214.34+/-151.85 vs. 240.43+/-144.36, P<0.01; 193.24+/-72.64 vs. 208.05+/-61.97, P<0.01). Conclusions: Our preliminary study demonstrated that the incidence of severe intraoperative complication during VATS lobectomy was low and similar to open lobectomy. The severe intraoperative complications during VATS lobectomy are manageable and the surgeons need to take proper caution in performing VATS lobectomy.