Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer's Disease (AD). APOE allele*3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the *4 allele is a well-established risk factor for CD, while the *2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD-type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18–35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele*2 presented better cognitive performance. The presence of allele*4 was associated with worse performance in a few executive tasks. APOE*3*3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD-type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.