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Background The role of renal function in patients with acute ischaemic stroke (AIS) receiving blood pressure (BP) lowering therapy remains incompletely understood. In this prespecified subgroup analysis of the CATIS-2 trial, we tested the hypothesis that baseline estimated glomerular filtration rate (eGFR) affects the relationship between early antihypertensive therapy and outcomes in AIS.Methods In the CATIS-2 trial, AIS patients were randomly assigned to early treatment (initiating BP-lowering agents within 24–48 hours of stroke onset) or delayed treatment (withholding such agents until day 8). The composite of functional dependence or death (modified Rankin Scale score ≥3) at day 90 was defined as the primary outcome. The treatment effect was analysed between different baseline eGFR values (<90 versus ≥90 mL/min per 1.73 m²).Results 4685 patients were finally enrolled. Among 1061 patients with eGFR<90, the risk of the primary outcome was higher in early treatment compared with delayed treatment (15.3% vs 10.5%; OR (OR) 1.55, 95% CI 1.07–2.23; p=0.02). In 3624 patients with eGFR≥90, no such difference was observed (10.7% vs 10.2%; OR 1.05, 95% CI 0.85 to 1.30; p=0.63). The interaction was marginally significant (p=0.07).Conclusions The modification effect of renal function on different antihypertensive timing for AIS was not observed. Further, adequately powered studies were warranted.Trial registration number NCT03479554.