No currently approved intervention counteracts airway metaplasia and mucus hypersecretion of Chronic Bronchitis (CB) in COPD. Metered Cryospray (MCS) delivering liquid nitrogen (LN2) to the tracheobronchial airways ablates abnormal epithelium and facilitates healthy mucosal regeneration. The objective of this study was to evaluate the feasibility, efficacy and safety of MCS in CB.Patients with a FEV1, 30-80% of expected, taking optimal medication were recruited. Primary outcomes: feasibility - completion of treatments; efficacy - 3-month change in St George's Respiratory Questionnaire (SGRQ); safety - incidence of adverse events (AEs).lung function, exercise capacity, additional patient-reported outcomes (PROs).35 patients, 19 male/16 female, aged 47-76 years, GOLD grade I (3), II (10) and III (22), underwent staggered LN2 treatments to the tracheobronchial tree.34 patients completed three treatments, each lasting 34·3±12·1 min, separated by 4-6 weeks: one withdrew after the first treatment. Approximately 1800 doses of MCS were delivered.Clinically meaningful improvements in PROs were observed at 3-months; ΔSGRQ -6·4 [95% CI -11.4, -1.3; p=0·01], COPD Assessment Test (CAT) -3·8 [95% CI -6.4, -1.3; p<0·01] and Leicester Cough Questionnaire (LCQ) 21·6 [95% CI 7.3, 35.9; p<0·01]. CAT changes were durable to 6-months (-3·4 [95% CI -5.9, -0.9; p=0·01]), SGRQ and LCQ to 9-months (-6·9 [95% CI -13.0, -0.9; p=0·03] and 13·4 [95% 2.1, 24.6; p=0·02], respectively).At 12-months, 14 serious AEs were recorded in 11 (31·4%) subjects, 6 moderate (43%) and 8 severe (57%). 9 were respiratory-related: 6 exacerbations of COPD, 2 pneumonias, and 1, increased coughing, recovered without sequelae. None were serious device or procedure-related AEs.MCS is safe, feasible and associated with clinically meaningful improvements in multidimensional PROs.