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Background The role of adiponectin (ADPN) in stroke remains debatable, despite its significant impact as a major adipocytokine on cardiovascular (CV) diseases. This study aimed to assess the association between ADPN and 5-year mortality, functional outcome and recurrence in Chinese individuals with first ischaemic stroke (IS).Methods This prospective, multicentre study recruited IS patients from 201 hospitals in China between August 2015 and March 2018. Multivariable Cox regression evaluated ADPN’s association with mortality/recurrence, while logistic regression analysed poor functional outcomes (modified Rankin Scale score 3–6 and 3–5).Results Among 8086 patients (median age 62; 31.8% female), there were 710 deaths, 1134 recurrences and 1223 poor functional outcomes (modified Rankin Scale 3–6). Higher baseline ADPN levels were significantly associated with increased risk of 5-year non-CV mortality (adjusted HR Q4 vs Q1=1.47 (95% CI 1.10 to 1.96), p=0.06) after adjustment for age, sex, body mass index and National Institutes of Health Stroke Scale. No independent associations were found between ADPN and CV mortality, stroke recurrence or poor functional outcome. Subgroup analysis revealed a significant association between ADPN and 5-year mortality from various causes among patients with cardioembolism (adjusted HR Q4 vs. Q1=2.39 (95% CI 1.24 to 4.62), p=0.007) and large artery atherosclerosis (adjusted HR Q4 vs Q1=2.16 (95% CI 1.34 to 3.47), p=0.004).Conclusions Elevated baseline ADPN levels were independently associated with increased 5-year non-CV mortality in Chinese IS patients, especially among those with mild neurological impairment. These findings suggest ADPN may serve as a prognostic biomarker for systemic vulnerability after stroke.