Background Anthracycline may cause heart failure in patients receiving chemotherapy. We investigate to determine N-acetylcystein(NAC), an antioxidant can prevent cardiac toxicity and heart failure. Methods A total of 104 patients were enrolled in this prospective randomized open label controlled trial. They are all patients firstly diagnosed to have cancer of breast or lymphoma or others who require chemotherapy. The chemotherapeutic agent (CA) included cardiac toxic adriamycin or epirubicin. Left side breast cancer which may require radiation therapy on breast overlapping heart shadow was excluded. Patients were randomized to NAC (n=50; 1200 mg orally every 8 hours starting before and ending after the intravenous infusion of cardiotoxic CA in all cycles[3-6] of chemotherapy) or placebo (n=54). Peak CK, CKMB, cTnI in each cycle and echocardiographic parameters at 3 month after completion of full chemotherapy cycles was compared. Clinical outcomes of death, heart failure and readmission were also compared between 2-groups. Results Breast cancer comprise of 94% of the study. Left ventricule(LV) ejection fraction(EF) at baseline were similar: 64.5% in NAC and 64.2% in control group. At 3month follow-up echocardiography, mean EF significantly decrease from the baseline to 55% (p=0.02) and 53.8% (p=0.01) in NAC and control. This change was similar in two groups: -9.5% and -10.4% (p=0.2) from the baseline. Both LV end systolic and end diastolic dimension was increase from 29.5짹5.2 to 36.2짹4.8mm (p=0.009) and from 45.5짹6.2 to 53.6짹5.5 mm in NAC group. Similar results was observed in control group: from 30.4짹5.6 to 38.2짹5.8mm (p=0.005) and from 46.6짹4.8 to 55.6짹5.5 mm (p=0.008). The net change of LV end systolic and end diastolic dimension from the baseline was not different between NAC and control (p=0.08). Clinical outcome at 1, 3, 6 and 12month were comparable in two groups. Cumulative 12month mortality rate was 8% and 1.9% in NAC and control group respectively with no difference (p=0.193) Conclusions Short- term use of NAC does not seem to be beneficial in preventing anthracycline induced cardiomyopathy. Further outcome trial is warranted.