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Abstract Background Acute kidney disease (AKD) evolves a spectrum of acute and subacute kidney disease requiring a global strategy to address. The present study aimed to explore the impact of AKD on the prognosis of ischemic stroke. Methods The Third China National Stroke Registry (CNSR-III) was a nationwide registry of ischemic stroke or transient ischemic attack between August 2015 and March 2018. As a subgroup of CNSR-III, the patients who had serum creatinine (sCr) and serum cystatin C (sCysC) centrally tested on admission and at 3-month, and with 1-year follow-up data were enrolled. Modified AKD criteria were applied to identify patients with AKD during the first 3 months post stroke according to the guidelines developed by the Kidney Disease: Improving Global Outcomes in 2012. The primary clinical outcome was 1-year all-cause death, and secondary outcomes were stroke recurrence and post stroke disability. Results Five thousand sixty-five patients were recruited in the study. AKD was identified in 3.9%, 6.7%, 9.9% and 6.2% of the patients by using sCr, sCr-based estimated glomerular filtration rate (eGFRsCr), sCysC-based eGFR (eGFRsCysC), and combined sCr and sCysC-based eGFR (eGFRsCr+sCysC) criteria, respectively. AKD defined as sCr or eGFRsCr criteria significantly increased the risk of all-cause mortality (adjusted HR 2.67, 95% CI: 1.27–5.61; adjusted HR 2.19, 95% CI: 1.17–4.10) and post stroke disability (adjusted OR 1.60, 95% CI: 1.04–2.44; adjusted OR 1.51, 95% CI: 1.08–2.11). AKD diagnosed by eGFRsCysC or eGFRsCr+sCysC criteria had no significant impact on the risk of all-cause death and post stroke disability. AKD, defined by whichever criteria, was not associated with the risk of stroke recurrence in the adjusted model. Conclusions AKD, diagnosed by sCr or eGFRsCr criteria, were independently associated with 1-year all-cause death and post stroke disability in Chinese ischemic stroke patients.