Objective：To evaluate the clinical efficacy of neoadjuvant endocrine therapy (NET) for multidrug resistant (MDR) proteins positive breast cancer. Methods：Sixty-two postmenopausal women with locally advanced breast cancer (LABC) and estrogen receptor (ER) and MDR protein positive were randomly devided into two groups: Neoadjuvant chemotherapy (NCT) group, receiving 4 courses of TEC (taxotere, epirubicin and cyclophosphamide) chemotherapy regimen, and NET group, receiving 3 months of letrozole therapy. The therapeutic effect of the two groups was compared. Results：The overall response ［OR, complete response (CR) + partial response (PR)］ rate and CR of NCT group was 58.8% (20/34) and 5.9% (2/34) evaluated by physical examination, and was 47.1% (16/34) and 2.9% (1/34) by ultrasonic method, respectively; no pCR was noted in the patients of NCT group. The OR and CR of NET group was 67.9% (19/28) and 28.6% (8/28) evaluated by physical examination, and was 57.1% (16/28) and 25.0% (7/28) by ultrasonic method, respectively; the pCR was 3.6% (1/28) in NET group. No significant difference was found in OR (both by physical examination and ultrasonic method) between NCT and NET group, but the CR (both by physical examination and ultrasonic method) of NET group was significantly higher than that of NCT group (P＜0.05), while breast-conserving rates of two groups were similar. Conclusions：NET with letrozole may be a preferable choice for ER (+) and MDR (+) postmenopausal patients with LABC.