Background and aims: Systemic immune-inflammation index (SII) has been recently investigated as a novel inflammatory and prognostic marker. SII may be used as an indicator reflecting the progressive inflammatory process in atherosclerosis, although its link to incident cardiovascular disease (CVD) has not been examined in previous studies. This study aims to prospectively assess the association of SII with incident CVD and its main subtypes in Chinese adults. Methods: Using data from the Dongfeng-Tongji cohort study, 13,929 middle-aged and older adults with a mean age of 62.56 years (range 35?91 years), who were free of CVD and cancer, were included for analysis. The baseline study was conducted in Shiyan city, Hubei province from 2008 to 2009. The SII was calculated as platelet count (/L) ? neutrophil count (/L)/lymphocyte count (/L). Cox regression models were used to examine the associations of SII with incident CVD, including stroke and coronary heart disease (CHD). Results: Over a median 8.28 years (maximum 8.98 years) of follow-up, 3386 total CVD cases, including 801 stroke cases and 2585 total CHD cases, were identified. In multivariable Cox regression analyses, higher levels of log-transformed SII were significantly associated with total stroke (HR 1.224, 95% CI 1.065?1.407) and ischemic stroke (HR 1.234, 95% CI 1.055?1.442). For those participants with the highest quartiles of SII versus the lowest quartiles of SII, the HRs were 1.358 (95% CI 1.112?1.658) for total stroke, 1.302 (95% CI 1.041?1.629) for ischemic stroke, and 1.600 (95% CI 1.029?2.490) for hemorrhagic stroke. Conclusions: SII may serve as a useful marker to elucidate the role of the interaction of thrombocytosis, inflammation, and immunity in the development of cerebrovascular diseases in the middle-aged and elderly population.