Background Bronchodilators are used for managing the symptoms of chronic obstructive pulmonary disease (COPD) and minimizing the risk of hospitalization and readmission. Hospital readmission is predictive of morbidity and mortality. Objective The study objective was to compare all-cause readmission risk in COPD patients receiving nebulized long-acting β2-agonists (neb-LABAs) versus nebulized short-acting β2-agonists (neb-SABA) following COPD-related hospitalization discharge. Methods This retrospective analysis utilized US-based pharmacy and medical claims records (2001–2011) to identify COPD patients aged ≥40 years receiving neb-LABA or neb-SABA treatment within 30 days following discharge from a COPD-related hospitalization. Patients had to be continuously enrolled in their health plan for ≥6 months before and after their first neb-LABA or neb-SABA prescription fill (index date), and adherent to the treatment for the first 3 months post-index date. To select patients with similar severity profiles, neb-LABA and neb-SABA patients were matched by baseline characteristics. Readmission risks were observed over the 6-month period following the index date and compared between neb-LABA and neb-SABA cohorts using the multiple variable Cox proportional hazards model. Results The analysis included 246 matched patients (neb-LABA = 123; neb-SABA = 123). The mean age was 67 years, and 54% were female. The average length of stay during index hospitalization was 4.4 days. After adjusting for potential confounders, the risk of readmission was 47% lower in the neb-LABA cohort than in the neb-SABA cohort (hazard ratio 0.53, 95% confidence interval 0.30–0.96; P = 0.0349). Conclusions Patients receiving neb-LABAs had a significantly lower readmission risk within 6 months following a COPD-related hospitalization versus patients treated with neb-SABAs.