Objective To investigate the association between potentially inappropriate medication (PIM) and comorbidity, frailty and disability in the hospitalized elderly inpatients. Methods Selected for the study were 372 inpatients aged ≥65 years old in the Integrated Department of Fu Xing Hospital of Capital Medical University from June 2016 to June 2017. According to the PIM list for the elderly Chinese (version 2017), the patients were divided into PIM group (n=238) and non-PIM group (n=134), and data were recorded of their general information, comorbidity, and Charlson comorbidity index (CCI), frailty and disability. SPSS statistics 23.0 was used to process data. Independent sample t-test, nonparametric test or χ² test was performed. Spearman correlation analysis was made to explore correlation between PIM and comorbidity, frailty and disability. Multivariate logistic regression was done to analyze the risk factors associated with PIM. Results The incidence of PIM was 64.0%(238/372), with top three being clopidogrel 27.2%(101/372), eszolam 26.9%(65/372) and rabeprazole 14.8%(55/372). Compared with the non-PIM group, the PIM group were more advanced in age and number of prescribed medicines, had higher frailty score and CCI, and greater decline in the 6-m walking speed , but lower ADL and IADL. The difference was statistically significant (P<0.05). Spearman correlation analysis showed that PIM positively correlated with age (r=0.152, P=0.003), drugs number (r=0.493, P<0.001), CCI (r＝0.126, P＝0.015), decline in 6-m walking speed (r＝0.110, P=0.034) and frailty scale (r＝0.141, P=0.006) but negatively correlated with ADL (r＝-0.131, P=0.011) and IADL (r＝-0.128, P=0.014). Multivariate logistic regression suggested that the drugs number was a risk factor for PIM (OR=1.604,95%CI 1.427-1.804;P<0.001). Conclusion The number of drugs administered is a risk factorfor PIM in the elderly inpatients, and accordingly, clinicians should pay more attention to PIM by strengthening rationality in medication and minimize the number of prescribed drugs.