Objectives: The purpose of this study was to systematically assess existing studies to demonstrate the association between potentially inappropriate medication (PIM) and frailty.

Design: Systematic review and meta-analysis.

Methods: We searched major electronic databases (PubMed, Web of Science, the Cochrane Library, Embase, CINHAL, PsycInfo, China National Knowledge Infrastructure, China Biology Medicine disk, Weipu, and Wanfang) from their inception until February 25, 2023 (data updated on May 4, 2023), for observational studies investigating PIM and frailty. I(2) was used to measure the heterogeneity between studies quantitatively. A random effect model calculated pooled effect size owing to high heterogeneity. Subgroup analysis was conducted to explore sources of heterogeneity. Additionally, the studies' quality was evaluated using the Newcastle Ottawa Scale (a modified Newcastle Ottawa Scale was used to evaluate cross-sectional studies).

Results: Twenty-four studies were included for systematic review, 14 of which were included in the meta-analysis. After pooling the effect size, the odds ratio with PIM as the dependent variable was 1.12 (95%CI: 1.01-1.25), and that with frailty as the dependent variable was 1.75 (95%CI: 1.25-2.43), indicating a bidirectional association between PIM and frailty.

Conclusions: PIM and frailty interact with each other and have a bidirectional association, thus providing additional information for early clinical identification and prevention of frailty, and medication safety management.