Background: Anti-HER2 monoclonal antibody is associated with a greater risk of heart failure (HF) in female breast cancer patients. In recent years, the indication of anti-HER2 monoclonal antibodies was further expanded to stomach, colorectal, and salivary gland cancers regardless of sex in Japan. However, there have been no data on sex difference in the risk of HF after the anti-HER2 monoclonal antibody treatment. Objectives: We compared the risk of HF between male and female cancer patients treated with anti-HER2 monoclonal antibody using a nationwide population-based database. Method: We analyzed 4608 cancer patients (230 men, median age;52 years, breast cancer;4333) treated with HER2 monoclonal antibody enrolled in the JMDC Claims Database. The primary outcome was the incidence of HF. Results: Over a mean follow-up of 917±835 days, 559 HF events were documented. Kaplan-Meier curves showed no significant difference in the incidence of HF between men and women. Multivariable Cox regression analysis showed that male sex was not associated with a risk of HF compared with women (HR:0.76 95% CI:0.39-1.49). Conclusions: Our analysis of a nationwide population-based database firstly revealed that no significant sex difference existed in the risk of HF among cancer patients treated with anti-HER2 monoclonal antibody. Our findings suggest that the use of anti-HER2 monoclonal antibodies in male patients may be associated with similar risks observed in female patients.