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Background/Objectives Post-stroke cognitive impairment (PSCI) is an important yet overlooked consequence of stroke that negatively impacts quality of life. While the MMSE and MoCA are frequently used, they are not domain-specific and do not evaluate stroke-specific cognitive deficits. Of the domain-specific tests, there is still a dearth of knowledge regarding the validity of the Addenbrooke’s Clinical Examination III (ACE-III) for the detection of PSCI after a first-ever stroke.Methods Patients without prior cognitive impairment were prospectively recruited within 7 days of an acute first-ever stroke. Patients exhibiting impairment on ≥1 domain on the stroke-specific Oxford Cognitive Screen (OCS) were diagnosed with PSCI. The discriminatory capacity of the ACE-III to detect PSCI and domain-specific impairments as determined by the OCS was assessed.Results The OCS detected PSCI within 7 days of a first-ever stroke in 70% of the 30 patients that were recruited. The total ACE-III score could discriminate between normal cognition and PSCI as detected by the OCS ( AUC=0.897), with a sensitivity of 85.7% and specificity of 77.8%. The ACE-III did not detect any cognitive impairment in five patients with PSCI as diagnosed by OCS. Conversely, two patients with aphasia were classified with PSCI on ACE-III but were cognitively intact by the OCS.Conclusion/Decision While the total ACE-III score held discriminatory capacity between normal cognition and PSCI, its measures of accuracy may not be adequate for clinical use in the acute stroke setting. The OCS may be useful for identifying patients with domain-specific functional impairments that benefit from early intervention.