Background: Breast cancer is the most common cancer diagnosed in women. Cardiovascular diseases (CVD), alternatively, is the leading cause of mortality in women worldwide. Adjuvant endocrine therapy including AI and SERM is offered to almost 75% of patients with estrogen receptor–positive (ER⁺) disease and potentially raises concerns for negative effects in cardiovascular health. Our study aims to evaluate cardiac events including acute coronary syndrome (ACS) and heart failure requiring hospitalization (HF) in post-menopausal patients treated with AI and SERM. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Development of ACS and heart failure requiring hospitalization upon initiating AI or SERM was considered an adverse cardiac event. Statistical analysis was performed with SAS v9.4. software. Chi Square (or Fisher’s Exact test) was used to test associations between various medication and cardiac events. Student’s T-test (or non-parametric equivalent when violations occurred) was used to assess if there was a difference in delta between those on and those not on medication categories. All significance was assumed at the p < 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Of the 336 patients, 55% (n = 185) and 22% (n = 77) were offered therapy with AI and SERM, respectively. 6.49 % (n = 12) developed cardiac event with AI compared to 7.10 % (n = 13) who were not on AI therapy, (p = 0.814). Similarly, 6.49 % (n = 5) developed cardiac event with SERM compared to 6.87 % (n = 20) who were not on SERM therapy, (p = 0.9064). Moreover, an interesting finding in patients treated with SERM therapy compared to those not on SERM therapy was the delta of left ventricular ejection fraction (LVEF). Median LVEF of 3.5% (0 to 21%) was noted in patients treated with SERM compared to a median LVEF of 5% (0 to 55%) in patients who were not treated with SERM, p = 0.048. Conclusions: Our findings revealed AI and SERM therapy did not increase adverse cardiac events in our patient cohort. Cardiac safety of the patients is less likely to be compromised with AI and SERM therapy and therefore, should be initiated early in the course of treatment for better patient outcome. Furthermore, since SERM therapy can possibly have an effect in the LVEF of patients, a frequent evaluation LVEF is warranted to prevent any unwarranted complications.