To investigate the safety and outcomes of Z-palatopharyngoplasty (ZPPP) combined with endoscopic Coblator open tongue base resection (Eco-TBR) for the treatment of severe obstructive sleep apnea/hypopnea syndrome (OSAHS). Review of a prospective database. Academic tertiary medical center. Thirty-nine patients with severe OSAHS who had multilevel obstruction, failed continuous positive airway pressure therapy, and then underwent ZPPP plus Eco-TBR were enrolled in this study. The subjective symptoms and objective polysomnography parameters were collected preoperatively and at a minimum of 12 weeks postoperatively. Statistical analysis was determined by the Wilcoxon signed rank test. Thirty-five patients, consisting of 3 female and 32 male patients (mean age, 42 years), had completed data for final analysis. None of the patients had perioperative or postoperative serious complications. The classical success rate was 62.9% (22/35). Three months postoperatively, the Epworth Sleepiness Scale decreased from 11.0 ± 4.2 to 8.7 ± 4.3 (P = .0006). The mean apnea/hypopnea index decreased from 50.6 ± 16.6 to 26.5 ± 23.5 events/h, the lowest oxygen saturation (%) improved from 70.4 ± 9.9 to 80.1 ± 11.3, and the snoring visual analog scale (0-10) as assessed by bed partner decreased from 9.86 ± 0.69 to 3.27 ± 1.96 (P < .0001 for all variables). This study shows the significant benefits of ZPPP plus Eco-TBR in patients with severe OSAHS.