IMPORTANCE: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. OBJECTIVE: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index BMI >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. INTERVENTIONS: There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min interquartile range {IQR}, 0.5-2.0 L/min) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min IQR, 0.5-1.5 L/min). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. MAIN OUTCOMES AND MEASURES: Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. RESULTS: A total of 116 patients (mean SD age of 67 10 years, 53% female, mean BMI of 21.6 IQR, 18.2-26.1, mean SD forced expiratory volume in the first second of expiration of 0.6 L 0.2 L, and mean SD Paco2 while breathing room air of 59 7 mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. CONCLUSIONS AND RELEVANCE: Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00990132