Background: The relative value of trastuzumab (H) monotherapy as an adjuvant treatment compared to the standard combination treatment with chemotherapy (CT) is not clear for elderly breast cancer (BC) patients (pts). Methods: We randomly assigned pts over 70 years (yrs) old with HER2-positive invasive BC who received curative surgery into either H (H group) or H plus CT (H+CT group) selected from pre-specified regimens (PTX/DTX/TC/AC/EC/FEC/CMF/TCb [CBDCA]). The primary endpoint was disease-free survival (DFS), and the total required numbers of events and pts were set to 120 and 260, respectively, for assuring a statistical power of 80% for a 95% confidence interval (CI) with a hazard ratio (HR) of H to H+CT not to exceed 1.69. Restricted mean survival time (RMST) was calculated as a supplementary endpoint for interpreting the relative benefit of H because the blinded interim analysis showed the number of events was much fewer than expected, and the statistical power of the non-inferiority test based on HR is not assured. Results: A total of 275 pts were randomized from 2009 to 2014. The median age was 73.5 (70-80) yrs and the median follow up time was 3.52 yrs. Stage I (pT > 0.5cm) 43.6%, IIA 41.7%, IIB 13.5%, IIIA 1.1%. The planned analysis showed that DFS at 3 yrs was 94.8% in H+CT (n = 131, 12 events) vs 89.2% in H (n = 135, 18 events) (HR = 1.42; 95% CI, 0.68 to 2.95, P = 0.35). The difference in RMST between arms at 3 yrs was 0.45 months (mo). Relapse-free survival at 3 yrs was 95.6% (9 events with 4 deaths) in H+CT vs 91.7% (13 events with 5 deaths) in H. Common adverse events (AE) in H+CT vs H were anorexia (44.3% vs 7.4%, P < 0.0001), alopecia (71.8% vs 2.2%, P < 0.0001) and grade 3/4 non-hematological AE were 29.8% vs 11.9% (P = 0.0003). The total score of FACT-G improved more in H at 12 mo (H: 42.9% vs H+CT: 25.3%, P = 0.021). Conclusion: Small number of events precluded the evaluation of H monotherapy based on HR of DFS, and comparison of RMSTs revealed the lost survival due to omitting CT was less than 1 mo at 3 yrs. In light of less toxicity and a better QOL profile, H monotherapy can be an option as an adjuvant therapy for elderly HER2-positive BC pts. Clinical trial information: NCT01104935