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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., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)