Carotid endarterectomy (CEA) is a surgical procedure to remove stenotic atherosclerotic plaque from the origin of the carotid artery to reduce the risk of major stroke. Its impact on post-operative cognitive function (POCF) remains controversial, complicated in part by a traditional failure to account for practice effects incurred during consecutive psychometric testing. To address this for the first time, we performed psychometric testing (learning and memory, working memory, attention and information processing and visuo-motor coordination) in 15 male patients aged 68 ± 8 years with symptomatic carotid stenosis the day before and 24 hours following elective CEA (2 consecutive tests, 48 hours apart). Multiple baselining was also performed in a separate cohort of 13 educationally, anthropometrically and age-matched controls (63 ± 9 years) not undergoing revascularisation at identical time-points with additional measures performed over a further 96 hours (4 consecutive tests, each 48 hours apart). A single consecutive test in the control group resulted in progressive improvements in learning and memory, working memory, attention and information (P < 0.05 vs. Test 1) with 3 tests required before cognitive performance stabilised. Following correction for practice effects in the patient group, CEA was associated with a deterioration rather than an improvement in learning and memory as originally observed (P < 0.05). These findings highlight the potential for the clinical misinterpretation of POCF unless practice effects are taken into account and provide practical recommendations for implementation within the clinical setting.