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Background: Efforts to improve rural stroke care have intensified in China. However, high-quality comprehensive data on the differences in care and outcomes between rural and urban hospitals are limited. Methods: We analyzed data on patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals from 2015 to 2022. The in-hospital management measures assessed included nine acute and five discharge management measures. Outcomes evaluated included death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACE), disability at discharge, and in-hospital complications. Results: We enrolled 1,583,271 patients with acute ischemic stroke from 1930 hospitals, comprising 1086 (56.3%) rural sites with 735,452 patients and 844 (43.7%) urban sites with 847,891 patients. Patients in rural hospitals demonstrate suboptimal management measures compared to those in urban hospitals, including lower rates of intravenous recombinant tissue plasminogen activator within 4.5 h (26.0% vs 28.3%; difference: –2.3% (–2.5% to −2.0%)), endovascular treatment (0.6% vs 1.9%; difference: –1.3% (–1.3% to −1.2%)), vessel assessment (88.5% vs 92.0%; difference: –3.5% (95% confidence interval (CI): –3.6% to −3.4%)), and anticoagulants for atrial fibrillation at discharge (42.9% vs 47.7%; difference: –4.8% (95% CI: –5.4% to −4.2%)). Overall, the rural-urban disparity in in-hospital outcomes was small. Rural patients had a slightly higher rate of in-hospital death/DAMA (9.0% vs 8.0%; adjusted odds ratio (OR): 1.22 (95% CI: 1.20–1.23); adjusted risk difference (aRD): 1.3% (95% CI: 1.2%–1.4%)) and a slightly lower rate of complications (10.9% vs 13.0%; aOR: 0.83 (95% CI: 0.82–0.84); aRD: –1.3% (95% CI: –1.3% to –1.3%)). No notable rural-urban differences were observed in MACE and disability at discharge. Conclusion: Patients in rural hospitals demonstrated suboptimal management measures and had higher rates of in-hospital death/DAMA compared to those in urban hospitals. Prioritizing the allocation of health resources to rural hospitals is essential to improve healthcare quality and outcomes. Data access statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request. [ABSTRACT FROM AUTHOR]