Background: NACT for early breast cancer allows in vivo chemosensitivity testing. Primary results of this randomized, non-comparative 2-arm study have been published (Schneeweiss et al, Ann Oncol 2011). Here we provide 3-year follow-up data for disease-free survival (DFS) and safety. Methods: 257 patients (pts) with untreated operable T2–T4a–c N0–2 M0 breast cancer were randomly assigned to receive either four cycles of doxorubicin 60 mg/m² plus pemetrexed 500 mg/m² every 3 weeks (q3w) followed by four cycles of docetaxel 100 mg/m² q3w (AP-D; 135 pts), or four cycles of doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² q3w followed by four cycles of docetaxel 100 mg/m² q3w (AC-D; 122 pts). Both arms were stratified according to hormone receptor (HR) status (estrogen and/or progesterone receptor positive vs both negative) and study center. Surgery was carried out within 2 months after last chemotherapy. Primary objective was pathological complete response (pCR) rate in the breast (ypT0/is). Secondary objectives included long-term efficacy and safety measures. DFS and adverse event data were collected from all patients for 3 years or until progression or death. The Kaplan-Meier (KM) analysis technique and Cox regression method were used as statistical measures. KM analyses were performed on HR-positive and -negative pts subgroups. Results: As reported earlier, pCR rates were 16.5% for AP-D and 20.2% for AC-D. The 3-year DFS rate was 76% and 77% for AP-D and AC-D, respectively. Cox regression analysis for the overall enrolled population (regardless of treatment) revealed significantly longer DFS in HR-positive than in HR-negative pts (hazard ratio 0.35; 95% CI 0.22–0.58; p < 0.001). In HR-positive pts, the 3-year DFS rate was 88% (95% CI: 81–95%) with AP-D and 83% (95% CI: 74–91%) with AC-D. In HR-negative pts, the 3-year DFS rate was 55% (95% CI: 40–70%) for AP-D and 68% (95% CI: 53–82%) for AC-D. The 3-year follow-up data did not reveal any changes in the safety profile compared to the previously published results. Conclusions: The 3-year DFS rates of both NACTs are in line with published studies.