Environmental and genetic factors may both affect the risk of vascular cognitive impairment developing after a stroke. To identify factors affecting this risk, the cognitive status of 121 patients was examined 3 months after an ischemic stroke. In all patients and in 270 control subjects, 7 polymorphisms reported to affect risk of vascular ischemic disease were genotyped. In 51 patients (42.1%), vascular cognitive impairment resulted, defined by a Mini-Mental State Examination score of less than 24. These patients were older and more likely to be women. Alleles of none of the polymorphisms differed between patients with or without vascular cognitive impairment, except for glutamate-cysteine ligase modifier (GCLM) (odds ratio = 2.8, P = .006). When all stroke patients were considered, the GCLM genotype did not affect Mini-Mental State Examination scores. Testing the GCLM genotype in an independent group of stroke patients may determine whether this association with vascular cognitive impairment is genuine.