Chronic obstructive pulmonary disease (COPD) stands as one of the leading causes of mortality worldwide. Acute exacerbations of COPD (AECOPD) lead to rapid respiratory function decline and worsened disease status. Despite recent studies, the ability of the neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in patients with COPD remains controversial. We investigated the predictive value of NLR for adverse outcomes in hospitalized patients with AECOPD. A retrospective study was conducted at the Department of Pulmonary Medicine, Cho Ray Hospital (Vietnam) from November 2019 to November 2021. The study extracted data from patients diagnosed with AECOPD at discharge and met the inclusion criteria. NLR is calculated by dividing the number of neutrophils by the number of lymphocytes in the peripheral blood test. Adverse outcomes are defined as invasive mechanical ventilation, admission to intensive care unit, or in-hospital mortality. Multivariable regression analysis was conducted to identify variables predicting adverse outcomes. The cutoff, sensitivity, specificity, area under the curve, and receiver operating characteristic of NLR were determined for predicting adverse outcomes. Two hundred eighty-seven patients with AECOPD were included in the final analysis, with a mean age of 70.9, and males comprising 92.7%. The rate of adverse outcomes was 15.7%. Multivariable logistic regression identified reduced consciousness at admission (adjusted odds ratio = 0.08, 95% confidence interval [CI]: 0.02–0.38, P = .001) and high NLR (adjusted odds ratio = 1.17, 95% CI: 1.10–1.24, P < .001) as predictors of adverse outcomes. The receiver operating characteristic of NLR’s predictive value yielded an area under the curve of 0.877 (95% CI: 0.83–0.93). An NLR cutoff of 11.0 predicted adverse outcomes with a sensitivity of 80.0%, specificity of 77.7%, and an odds ratio of 13.9 (95% CI: 6.3–30.7), P < .001. NLR is a simple, routine, and cost-effective tool for predicting adverse outcomes in hospitalized patients with AECOPD. Future studies should evaluate the kinetics of NLR in predicting treatment response in patients with AECOPD.