OBJECTIVE： To compare the effects of prophylactic application of 3 different antibiotics on prognosis in patients underwent breast lesion resection. METHODS： 1 066 patients with breast lasion resection from 12 hospitals of Shaanxi province were divided into trial group （360 cases）， control group A （352 cases） and control group B （354 cases） according to random number table. Trial group was given first generation cephalosporin cefazolin； control group A was given second generation cephalosporin cefuroxime； control group B was given third generation cephalosporin cefoperazone sodium and tazobactam sodium. The dosage regimens of 3 groups were as follows： relevant drug 2 g added into 0.9％ Sodium chloride injection 100 ml， ivgtt， 0.5 h before surgery， medication course≤24 h after surgery in trial group. Those indexes of 3 groups were observed， such as post-operative ADR， incision healing， infection， hospitalization duration， phamaceutical costs per capita. RESULTS： There was no statistical significance in the rate of incision healing and the rate of post-operative infection among 3 groups （P＞0.05）. The incidence of post-operative ADR， hospitalization duration and phamaceutical costs per capita in observation group were significantly lower or shorter than in control group A and B， with statistical significance （P＜0.05）. CONCLUSIONS： Cefazolin is better than cefuroxime and cefoperazone sodium and tazobactam sodium to reduce the postoperative adverse reaction， antibiotics cost per capita and hospital drug cost per capita， shorten the hospitalization duration.