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ObjectiveTo investigate the clinical efficacy of the subxiphoid approach for early anterior mediastinal thymoma and evaluate its advantages over the lateral intercostal approach.MethodsA total of 345 patients with early anterior mediastinal thymoma were retrospectively analyzed from January 2016 to December 2020 in the First Affiliated Hospital of Soochow University. Out of these, 99 patients underwent subxiphoid video-assisted thoracoscopic thymectomy and 246 patients underwent transthoracic video-assisted thoracoscopic thymectomy. We compared the intraoperative conditions (such as operation time and intraoperative blood loss), postoperative conditions [such as postoperative pleural drainage volume, extubation time, postoperative hospital stay, and postoperative visual analogue scale (VAS) pain score], and postoperative complications (such as death, pneumonia, delayed wound healing, cardiac arrhythmia, and phrenic nerve injury) of the two groups and analyzed the clinical advantages of the subxiphoid approach for treating early anterior mediastinal thymoma.ResultsThere was no significant difference between the two groups in terms of general clinical features, operation time, and postoperative complications (P > 0.05).However, there was a significant difference in terms of intraoperative blood loss, postoperative pleural drainage volume, tube extubation time, postoperative hospital stay, postoperative VAS pain score, and postoperative analgesics (a significantly decreased flurbiprofen axetil amount) (P ConclusionCompared with the lateral intercostal thoracic approach, the subxiphoid approach had advantages in terms of intraoperative blood loss, postoperative hospital stay, tube extubation time, postoperative pleural drainage volume, postoperative VAS pain score, and analgesics dosage. It could provide a better view of the bilateral pleural cavities and more thorough thymectomy and superior cosmesis, and it proved to be a safe and feasible minimally invasive surgical method.