Background: Post-stroke cognitive impairment (PSCI) occurs commonly and is linked with development of dementia. We investigated the relationship between demographic, clinical and stroke symptoms at stroke onset and the presence of PSCI at 1 and 3 years after stroke. Methods: We accessed anonymized data from the Virtual International Stroke Trial Archive (VISTA), including demographic and clinical variables. Post-stroke cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤26. We assessed univariate relationships between baseline stroke symptoms and PSCI at 1 and 3 years following stroke, retaining the significant and relevant clinical factors as covariates in a final adjusted logistic regression model. Results: We analysed data on 5435 patients with recent (median 33 days) stroke or transient ischaemic attack (TIA). Mean (±SD) age was 62.6 (±12.6) years; 3476 (65%) patients were male. Follow-up data were available for 2270 and 1294 patients at 1 and 3 years, respectively. At 1 year, 781 (34%) patients had MMSE≤26; at 3 years, 391 (30%) had MMSE≤26. After adjusting for age, stroke severity, hypertension, diabetes and type of qualifying event, initial stroke impairment (leg paralysis) was associated with increased rate of PSCI at 1 year (OR=1.62; 95% CI=1.20–2.20) and at 3 years (OR=1.95; 95% CI=1.23–3.09). Associations were consistent on subgroup analysis restricted to ischaemic stroke and transient ischaemic attack (N=4992). Conclusions: Besides well-known determinants of PSCI such as age, stroke severity and the presence of vascular risk factors, also leg paralysis is associated with subsequent of PSCI up to 3 years after stroke.