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Background: Studies revealed unidirectional associations between frailty and medication‐related problems (MRPs) among older adults. Less is known about the association between frailty and the risk of MRPs. We aimed to assess the bi‐directional association between frailty and the risk of MRPs in community‐dwelling older adults in five European countries. Methods: Participants were 1785 older adults in the population‐based Urban Health Centres Europe project. Repeated assessments were collected at baseline and one‐year follow‐up, including frailty, the risk of MRPs, and covariates. Linear regression analyses were conducted to examine the unidirectional associations. A cross‐lagged panel modeling was used to assess bi‐directional associations. Results: The unidirectional association between frailty at baseline and the risk of MRPs at follow‐up remained statistically significant after adjusting for covariates (β = 0.10, 95%CI:0.08, 0.13). The association between the risk of MRPs at baseline and frailty at follow‐up shows similar trends. The bi‐directional association was comparable with reported unidirectional associations, with a stronger effect from frailty at baseline to the risk of MRPs at follow‐up than reversed path (Wald test for comparing lagged effects: p < 0.05). Conclusion: This longitudinal study suggests that a cycle may exist where older adults with higher frailty levels are more likely to have a higher risk of MRPs, which in turn contributes to developing a higher level of frailty. Further research is needed to validate our findings and explore underlying pathways. [ABSTRACT FROM AUTHOR]