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Background: The neuroimaging evaluation of isolated third nerve palsy in adults remains controversial. We aim to define diagnostic yield for neuroimaging of third nerve palsy (TNP) by degree of internal and external dysfunction using previously published imaging guidelines., Methods: All cases of TNP evaluated at a tertiary care center between 1990 and April 2004 were reviewed. Inclusion criteria were neurologically isolated TNP in adults with adequate documentation of the ocular examination, neuroimaging, and follow-up. Exclusion criteria were neurologically non-isolated TNP, TNP occurring in children, and TNP secondary to a known etiology; lack of adequate follow-up; and insufficient documentation of the ocular exam. Published imaging guidelines based on degree of external and internal dysfunction were applied to our cohort to determine compliance with and the diagnostic yield of neuroimaging recommendations., Results: One hundred and eight cases were reviewed. Of the 91 excluded cases, there were 14 cases of aneurysm or subarachnoid hemorrhage. Of the 17 included cases, presumed ischemia (10), aneurysm (2), and ocular myasthenia (3) were the most common causes of isolated TNP. Neuroimaging was performed in 16 cases (94.1%). The neuroimaging strategy was concordant with neuroimaging recommendations in 7 cases (41.2% concordance). Failure to perform noninvasive angiography accounted for 7 cases (70.0%) of nonconcordance. The diagnostic yield of all neuroimaging studies performed was 68.8%; diagnostic yield in cases concordant with published neuroimaging recommendations was 100%., Interpretation: The degree of external and internal dysfunction can direct the type of neuroimaging performed in TNP.