Some patients with chronic obstructive pulmonary disease (COPD) have eosinophilic inflammation which may be evaluated via the measurement of fractional exhaled nitric oxide (FeNO) like asthma. The aim of this prospective study was to assess whether FeNO levels can be used to identify patients with COPD with eosinophilic inflammation who may respond to inhaled corticosteroid (ICS) therapy.This study included patients (N = 112) with COPD (age >18 years) who were divided into 4 groups depending upon whether they had high (≥25 parts per billion [ppb]) or low (<25 ppb) pretreatment (baseline) FeNO and if they were treated with either ICS plus long-acting β-agonist (ICS + LABA) or a long-acting muscarinic antagonist (LAMA). The 4 groups were: high FeNO/ICS + LABA, high FeNO/LAMA, low FeNO/ICS + LABA, and low FeNO/LAMA. Outcomes assessed included FeNO, COPD assessment test (CAT), and pulmonary function.The high FeNO/ICS + LABA group had the greatest reduction from baseline in FeNO levels (-25.80 ppb ± 27.14) compared with the high FeNO/LAMA, low FeNO/ICS + LABA, and low FeNO/LAMA groups (range, -4.45 to 1.31 ppb; P < .001). The high FeNO/ICS + LABA group also showed the greatest improvement in CAT (-7.20), which was statistically larger than the low FeNO/ICS + LABA and low FeNO/LAMA groups (-1.72 and -2.03, respectively). No difference in pulmonary function following treatment was observed across the 4 groups.This study found that patients with high FeNO showed the greatest reduction in FeNO and improvement in CAT with ICS + LABA therapy, supporting the use of FeNO to identify patients who would benefit from ICS use.