Although endoscopic thoracic sympathectomy (ETS) offers permanent cure of palmar hyperhidrosis (PH), compensatory hyperhidrosis (CH) often complicates the procedure. We analyzed the outcomes of a 2-month interval for unilateral sequential ETS (S-ETS) in comparison with simultaneous bilateral ETS (B-ETS), notably regarding CH and associated plantar hyperhidrosis, in treating patients with PH.Four hundred seven patients with intractable PH were randomly assigned into two groups: the B-ETS group (204 patients) and the S-ETS group (203 patients).Three hundred sixty-four patients completed the study. Complication rates were comparable for both groups. No patient died perioperatively, and no conversion was necessary. Treatment success on follow-up was 97.2% for S-ETS and 96.7% for B-ETS. The incidence of CH was decreased substantially from 131 (71.1%) patients in the B-ETS group to 22 (12.2%) patients in the S-ETS group (P<.001), with no patient suffering severe CH in the S-ETS group compared with 33 (25.5%) patients in the B-ETS group. Eighty-four (58.3%) patients in the S-ETS group had simultaneous disappearance or decreased perspiration on the soles. All patients in the S-ETS group were satisfied, whereas 37.9% of B-ETS patients were unsatisfied with their operation, mostly because of CH and recurrences.Although both sympathectomies were effective, safe, and minimally invasive methods for treatment of PH, unilateral sequential ETS appeared to be a more optimal technique in terms of reduction of CH to a minimum and improvement of associated plantar hyperhidrosis.