BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ(2) test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.