Object. Video-assisted thoracoscopic sympathectomy is a safe, effective, and minimally invasive procedure for primary hyperhidrosis. This study aims to evaluate long-term results and patients' quality of life and investigate potential variables responsible for compensatory sweating after one-stage bilateral single-port thoracoscopic sympathectomy. Methods. Between 2005 and 2011, 260 consecutive bilateral thoracoscopic sympathectomies were performed in 130 patients for primary palmar and axillary hyperidrosis through one-port access. Residual pain, postoperative complications, recurrence of symptoms, heart rate adjustment, and quality of life were analyzed. Multivariate analysis was performed. Results. No operative mortality and conversion to open surgery were recorded. Mean operative time was 38 ± 5 minutes. Mean hospital stay was 1.1 ± 0.6 days. Eight patients (6%) had unilateral pneumothorax. Twenty-five cases (19%) were complicated by compensatory sweating. Winter and fall were identified as protective factors for compensatory sweating occurrence. Decreased heart rate was observed 1 year after surgery and permanently over the time. No recurrence during the follow-up period (31.5 months) was observed and 90% of patients showed improved quality of life. Conclusions. One-stage bilateral miniuniportal thoracoscopic sympathectomy is a valid and safe treatment for primary hyperhidrosis, achieving definitive and esthetic results, with excellent patients' satisfaction. Compensatory sweating may potentially occur in a season-dependent manner.