AIMS: Previous studies have suggested an association between retinal artery occlusion (RAO) and ischaemic stroke (IS), both associated with elevated inflammatory factors. However, the role of high-sensitivity C-reactive protein (hs-CRP) in the sequential onset of these two diseases is still unclear. Based on this evidence, we evaluated the association of hs-CRP with RAO and IS. METHODS: We examined hs-CRP from both the large multicentre cohort study UK Biobank and Chinese Retinal Artery Occlusion study. Cox proportional hazard models were used to study the association of hs-CRP with incident RAO and IS during the long-term follow-up in the UK Biobank. Logistic regression analysis was employed to assess the cross-sectional relationship between hs-CRP with RAO and IS in the Chinese cohort. A restricted cubic spline (RCS) approach was employed to evaluate potential non-linear associations of hs-CRP with IS. RESULTS: After exclusions, the analysis included 459 188 participants from the UK and 338 participants from China. Over a median follow-up of 12.2 years, 136 cases of incident RAO and 3206 cases of incident IS events were recorded in the UK Biobank. After multivariable adjustment, higher hs-CRP (per 10 mg/L) level was associated with increased risks of RAO (HR: 1.34, 95% CI: 1.01 to 1.76) and IS (HR: 1.24, 95% CI: 1.17 to 1.33). RCS analysis revealed a significant non-linear relationship between hs-CRP levels and incident IS (P CONCLUSIONS: Our findings underscore hs-CRP as a robust risk factor for both RAO and IS. Controlling hs-CRP levels might reduce the incidence of RAO and secondary stroke.