Background: We examined the effects of surgery type and adjuvant chemotherapy on change in early-stage breast cancer patients’ quality of life (QOL) over time. Methods: A cohort of 549 patients (33.5 % ductal carcinoma in situ, 66.5 % stages I/IIA) were interviewed a mean 6.1 weeks (Time1), and 6.2 (Time2), 12.3 (Time3), and 24.4 (Time4) months following definitive breast-conserving surgery (BCS) or mastectomy. QOL was measured using the total Functional Assessment of Cancer Therapy-Breast (FACT-B). Adjusting for demographic, psychosocial, and clinical variables, multiple linear regression models estimated the associations between QOL and each of surgery type, chemotherapy, and their 2-way interaction at each interview. Adjusted generalized estimating equation (GEE) models tested Time1–Time4 change in QOL. Results: At Time2, chemotherapy (P < .001) and BCS (P < .001) were independently associated with worse QOL in adjusted linear regression, and the adverse effect of chemotherapy was prominent among patients who received BCS compared with those who received mastectomy (Pinteraction = .031). In the GEE model, QOL significantly improved over time among patients who received BCS (Ptrend = .047), mastectomy (Ptrend = .024), and chemotherapy (Ptrend < .001), but not among patients who did not receive chemotherapy (Ptrend = .720). All patients completed adjuvant chemotherapy and radiation by Time3. Regardless of surgery type, patients receiving chemotherapy reported lower QOL following surgery, and QOL improved after completion of adjuvant treatment. Conclusions: Chemotherapy had a short-term negative impact on QOL after definitive surgical treatment regardless of surgery type. QOL rebounded after completion of adjuvant treatment.