Studies suggest that adjuvant chemotherapy for early stage breast cancer (BC) is associated with cognitive impairment related to attention, memory, and visuospatial functioning. However, other studies have failed to confirm that relationship. We report one of the first longitudinal, controlled studies of cognitive effects of chemotherapy in older post-menopausal women. Sixty-one post-menopausal women with non-metastatic BC were administered neuropsychological tests before adjuvant therapy (Time1), six months after treatment (Time2), and at a final 6-month follow-up (Time3). Thirty women were treated with chemotherapy; thirty-one women who received no chemotherapy were controls. Cognitive domains measured included motor, language, attention/concentration/working memory, visuospatial, and memory (verbal and visual). Time-by-treatment interaction was significant in the motor domain (P = 0.007) with poorer performance in women treated with chemotherapy. For the other domains, scores did not significantly vary over time by group. In post-menopausal women, chemotherapy was not associated with changes in cognitive function in areas reported by BC survivors: attention, memory, and information processing. Motor slowing in women treated with chemotherapy could be secondary to peripheral neuropathy rather than an indication of more general declines in cognitive processing. Future studies should control for the independent effects of slowed motor functioning when looking to study possible chemotherapy related cognitive processing deficits.