Objective: The aim of this study was to evaluate the safety and ef iciency of combination of trastuzumab and che-motherapy as first line regimen in Her-2 overexpressing metastatic breast cancer (MBC) patients. The primary endpoint was overal response rate (ORR) and the second endpoint was clinical benefit rate (CBR) and toxcities. Methods: Estrogen recep-tor (ER) (–), progesterone receptor (PR) (–), Her-2 (+++) patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group (H group) and 75 of them were assigned to the Control group (C group). They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results: Response rate (RR) of the H group and the C group were 51.0% and 24.0% separately, and the dif erence were statistical y significant (P< 0.05). CBR of the two groups were 76.4% (H group) and 64.0% (C group), had significant dif erence (P < 0.05). Complete response rate (CRR) of the two groups were 21.5% and 6.6%, there were no significant dif erence between the two groups (P= 0.055). Grade 3–4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy (17.6%) and 4 patients with chemotherapy (5.4%), with no statistical significance (P = 0.054). In the subgroup of antharcycline-containing regimens, Grade 1–4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracycline contained chemotherapy (H + ACCT arm; 40.9%, 9/22)], and 4 patients in the antharcycline-containing chemotherapy arm (ACCT arm; 12.5%, 4/32). There was statistical significant dif erence between the two arms (P < 0.05). Grade 3–4 cardiac toxicity, the occurance rates were 18.1% (4/22) in H + ACCT arm and 6.3% (2/32) in ACCT arm, and there was no significant statistical dif erence (P = 0.352). Grade 3–4 granulocytopenia in the H group and C group were 27.5% (14/51) and 26.7% (20/75), with no significant dif erence (P = 0.922). Conclusion: The ef iciency of trastuzumab combining with chemotherapy using as first line regimen in Her-2 overexpressing MBC patients were exact. However, the long-term cardiac toxicity can be hidden troubles of trastuzumab using.