Background: Whether challenging video-assisted thoracoscopic surgery (VATS) is a minimal invasive surgery remains controversial. This study aimed to analyze causes of challenging conventional multiple-port VATS (CVATS) and conversion to thoracotomy and postoperative pain to provide indications for VATS., Methods: This was a two-center retrospective study. Challenging VATS was defined as CVATS with operation time ≥5 hours and it was converted to thoracotomy. This study included patients who were admitted to Joetsu General Hospital (Joetsu, Niigata, Japan) and Toyama University Hospital (Toyama, Japan) for elective CVATS between April 2013 and March 2019. The exclusion criteria were as follows: a planned thoracotomy, uniportal VATS, robot-assisted thoracoscopic surgery, and simultaneous resection of extrathoracic organs., Results: A total of 911 (91.6%) patients underwent CVATS. Of these cases, 876 (96.2%) were suitable VATS cases. On the contrary, 35 cases (3.8%) were recognized as challenging VATS. In 21 (2.3%) cases, VATS took ≥5 hours, and 14 (1.5%) VATS cases were converted to thoracotomy. The causes were severe adhesions (62.9%), air leak (45.7%), body position changes (22.9%), large tumor (14.3%), bronchoplasty or angioplasty (8.6%), and bleeding (2.9%). The minimum diameter of large tumors was 61.4 mm (53-67 mm). In 15 (71.4%) patients, VATS took ≥5 hours, and 10 (71.4%) patients who were converted to thoracotomy developed postoperative neuropathic pain., Conclusions: In this study, VATS ≥5 hours and conversion from VATS to thoracotomy were complicated by postoperative neuropathic pain. In case of bronchoplasty, angioplasty, and large tumor with minimum diameter ≥5 cm, a thoracotomy approach would be appropriate depending on the skill and experience of the surgeon. In cases of local or vascular sheath adhesion, if operation progress is delayed, it may be necessary to set a time limit and decide to convert to thoracotomy, considering patient's safety first.