The purpose of this study was to investigate the relations between regional white matter signal abnormalities (WMSA) and cognitive functioning among individuals being treated for cardiovascular risk factors and/or clinical events. Forty-one participants with cardiovascular disease underwent a comprehensive neuropsychological assessment and MRI. Total WMSAs were quantified using a semi-automated thresholding technique. Unique to this study, total WMSA volume was divided into three separate anatomically related regions: WMSA in the periventricular (PERIWMSA) region, WMSA adjacent to subcortical nuclei (SUBWMSA), and WMSA in the deep white matter (DEEPWMSA). A ratio of these measures to total cerebral brain volume was compared to cognitive measures assessing attention, executive functioning, psychomotor speed, immediate and delayed memory, language, and visuospatial functioning. PERIWMSA, SUBWMSA, and total WMSA were significantly associated with performance on measures of attention/processing speed. No other significant relationships between WMSA and cognition were noted. Secondary analyses suggested that PERIWMSA volume was increased in individuals with clinical evidence of atherosclerosis. These results emphasize the utility of studying the associations between regional WMSA and cognitive/functional performance in patients undergoing cardiovascular treatment.