Objective: To evaluate the clinical effect and prognosis of uniportal video-assisted thoracoscopic surgery (VATS) through the subxyphoid approach for bilateral bullae. Methods: 70 patients with bilateral bullae treated in this hospital during January 2014 to December 2015 were randomly divided into two groups. Patients in observation group (n=35) and control group (n=35) who underwent bilateral bullae excision with uniportal VATS were individually through the subxyphoid approach and the intercostal approach. The clinical indexes were compared between the two groups, including the surgery related indicators, the incidence of postoperative complications and the degree of pain, etc. Results: All operations were successfully completed; the observation group had shorter operation time. At 48 h, 72 h, and the 5th day after operation, the pain was less than that in the control group (P<0.05). The incidence of incision pain or incision numbness in observation group was significantly lower than that in control group during the 6-month follow-up period. But there was no significant difference in intraoperative blood loss, duration of postoperative thoracic tube drainage, total drainage volume and the incidence of postoperative complications between two groups (P>0.05). Conclusion: Simultaneous subxyphoid approach uniportal video-assisted thoracoscopic surgery for bilateral bullae is safe and feasible, which has shorter operation time, relief of postoperative pain and satisfying prognosis.