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Aims: We aimed to determine whether preprocedural renal function affects the outcome of acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT) and whether this effect is modified by the onset‐to‐reperfusion time (OTR) and mediated by collateral status. Methods: Eligible patients with anterior circulation large vessel occlusion (LVO) who underwent MT between August 2018 and August 2020 were reviewed. The main outcome was good functional outcome [defined as modified Rankin Scale (mRS) of 0–2] at 3 months. Multivariable logistic regression analyses were conducted to explore the relationship between renal function and good functional outcome. A moderation analysis and the Johnson‐Neyman technique were performed to assess the interaction between renal function and OTR to predict the outcome of AIS patients with MT. Results: Among 100 enrolled patients, 36 (36%) exhibited good functional outcome. A decreased preprocedural estimated glomerular filtration rate (pre‐eGFR) was significantly associated with worse functional outcome [adjusted OR, 1.059 (1.012–1.108); p, 0.014], and this effect was partly mediated by collateral circulation. An interaction between OTR and pre‐eGFR on functional outcome was observed (P for interaction, 0.22), and pre‐eGFR only had a significant effect on functional outcome when OTR exceeded 455.8 min. Moreover, the adverse effect of OTR on functional outcome became no longer significant when the pre‐eGFR was higher than 89.0 mL/min/1.73 mL/min/1.73 m². Conclusions: Renal function was related to functional outcome at 3 months, and this relationship could be modified by OTR. The results suggested that reducing OTR and improving collateral circulation may mitigate the adverse effect of reduced kidney function on functional outcome. [ABSTRACT FROM AUTHOR]