Background: The global randomized trials with trastuzumab (H) shows increased cardiotoxicity in patients (pts) with HER2 positive early breast cancer (BC). Safety in Japanese has not been fully evaluated. We evaluated the safety, especially focused on cardiotoxicity, of H adjuvant (adj) therapy in an observational study in Japan (UMIN000002737). Methods: Pts with histopathologically confirmed HER2 positive invasive BC were registered. Women with stage I-IIIC disease who received H as neo-adj and/or adj therapy were eligible. Mean LVEF at 3, 6, 9 and 18 months (M) was evaluated. The time points represent examination on day 60-120, 150-210, 240-330 and 455-635, respectively. Results: A total of 2024 pts were registered from 56 institutes between July 2009 and June 2011. Data of 1875 pts were collected and finalized by September 2012, and 1800 of them were analyzed for safety. The median follow-up was 35 M. The mean age was 54.5 years. Elderly pts ≥60 years were 32.7%. Treatments after surgery were: concurrent chemotherapy (CT) and H in 20.1%, sequential CT and H in 43.5% and H monotherapy in 35.9%. Adverse events (AEs) associated with H were reported in 350 pts (19.4%) and grade (G) 3/4 AEs in 12 pts (0.7%). G 3/4 cardiotoxicity was reported in 7 pts (dysfunction, 4pts; angina, 1 pt; myocardial infarction, 1 pt and heart failure, 1 pt). The mean LVEF at the baseline was 69.4%. Mean LVEF at 3, 6, 9 and 18M were 66.9%, 66.3%, 65.3% and 66.3%, respectively. Compared to the baseline, LVEF decreased with significant difference at all time points (p<0.0001). LVEF decrease ≥10% occurred in 177 pts (during H treatment,130 and after H treatment, 47). Follow-up data were available in 66 pts: 34 pts recovered to the baseline. Mean time to recover was 262 days. The univariate analysis showed using anthracycline (odds ratio 2.312, p=0.003) was the only risk factor for cardiotoxicity. However, elderly, radiation concurrent/sequential treatment with CT and H had no impact. Conclusions: From our study, we found the AE profiles of H were consistent with previously known AEs. We found using anthracycline was the risk factor for cardiotoxicity at the moment. We should carefully follow pts and watch long-term safety. Clinical trial information: 000002737.