The clinical implications of airflow limitation severity and blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and prolonged mechanical ventilation (PMV) are unknown. Thus, this study aimed to identify whether or not these two indicators were significantly associated with short-term in-respiratory care center (RCC) treatment outcomes in this population. Of all participants (n = 181) in this retrospective cross-sectional study, 41.4%, 40.9%, 8.3%, and 52.5% had prolonged RCC admission (RCC length of stay >21 days), failed weaning, death, and any adverse outcomes of interest, respectively. Compared to participants without any adverse outcomes of interest, moderate (the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II) and/or severe (GOLD III) airflow limitation were significantly associated with short-term in-RCC adverse outcomes in terms of failed weaning (for III versus I, OR = 15.06, p = 0.003) and having any adverse outcomes of interest (for II versus I, OR = 17.66, p = 0.002; for III versus I, OR = 37.07, p = 0.000) though the severity of airflow limitation did not have associations with prolonged RCC admission and death after adjustment. Meanwhile, blood eosinophilia defined by various cut-off values was not associated with any adverse outcomes. The findings have significant clinical implications and are useful in the management of patients with COPD and PMV.