Background: Recent studies draw different conclusions concerning whether omission of anthracyclines (A) in adjuvant chemotherapy for HER2-negative early breast cancer (EBC) may reduce toxicity without compromising efficacy. Methods: The prospectively randomized PlanB and Success C trials compared 6 cycles of docetaxel (D) and cyclophosphamide (C) with either 4 cycles of epirubicin (E) and C, followed by 4 cycles of D (EC-D, PlanB) or 3 cycles of 5-FU, E and C, followed by 3 cycles of D (FEC-D, SuccessC). Disease-free survival (DFS) was analyzed using univariable and multivariable Cox models adjusted for hormone receptor status (HRS) and histologic grade (G), age, menopausal status, type of surgery, pT, pN, and histologic type. Results: Overall, 5923 patients with follow-up data were available for this pooled analysis, with 2979 and 2944 patients randomized to A-free and A-containing chemotherapy, respectively. After 62 months median follow-up, DFS of patients receiving A-free vs A-containing chemotherapy was quite similar in univariable analysis (hazard ratio, HR = 1.04; 95% confidence interval, CI: 0.88 – 1.22, p = 0.64) and in multivariable analysis (HR = 1.00, 95% CI: 0.85 – 1.19, p = 0.96). Defining biological subtypes “luminal A-like” as HRS positive, G1/2, “luminal B-like” as HRS positive, G3, and TN (triple negative), no significant differences were seen in DFS between A-free and A-containing chemotherapy in luminal A-like (HR = 1.06, 95% CI 0.81 – 1.39, p = 0.66), luminal B-like (HR = 1.07, 95% CI 0.78 – 1.48, p = 0.68), or TN tumors (HR = 0.99, 95% CI 0.76 – 1.30, p = 0.95). However, in high-risk patients with four or more affected lymph nodes (pN2-3), A-containing chemotherapy was associated with significantly better DFS (HR = 0.69, 95%-CI 0.48- 0.98, p = 0.04). Conclusions: Our results suggest that 6 cycles of DC provide sufficient efficacy compared to an anthracycline-containing regimen in most patients with HER2-negative EBC. However, subgroup analyses indicate that high-risk patients might benefit from anthracycline-containing chemotherapy.