As the prevalence of chemotherapy-related cognitive impairment rises, investigation into treatment options is critical. The objectives of this study were to test the effects of an aerobic exercise intervention initiated during chemotherapy compared to usual care (wait list control condition) on (1) objectively measured cognitive function and self-reported cognitive function, as well as on (2) the impact of cognitive impairment on quality of life (QOL) postintervention (commensurate with chemotherapy completion). The Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial was a two-arm, two-center randomized controlled trial conducted in Ottawa and Vancouver (Canada). Fifty-seven women (Mage,48.8±10 years) diagnosed with stage I-III breast cancer and awaiting chemotherapy were randomized to aerobic exercise initiated with chemotherapy (nEX=28) or usual care during chemotherapy with aerobic exercise after chemotherapy completion (nUC=29). The intervention lasted 12-24 weeks and consisted of supervised aerobic training and at-home exercise. The primary outcome was objective cognitive function measured via 13 neuropsychological tests (standardized to M ± SD,0±1); secondary outcomes of self-reported cognitive function and its impact on QOL were assessed via questionnaires. Data collected pre- and postintervention (the primary end point) were analyzed. Although no significant differences between groups were found for objective cognitive function outcomes postintervention after accounting for multiple testing, four of six self-reported cognitive function outcomes showed significant differences favoring the aerobic exercise group. Among women initiating chemotherapy for breast cancer, aerobic exercise did not result in significant differences in objective cognitive function postintervention after chemotherapy completion; however, the results do support the use of this intervention for improving self-reported cognitive function and its impact on QOL.