Introduction: The external beam radiation therapy for patients with left breast cancer at the mastectomy site may cause myocardial perfusion abnormalities. We intended to study the change of these abnormalities at short and long term post radiotherapy follow up. Methods: Twenty patients with left and 20 patients with right breast cancer comprised the exposed and control groups, respectively. The patients had low risk for coronary disease. They underwent myocardial perfusion scans (MPS) 3 years after the external beam radiation therapy at the bed of modified radical mastectomy. These subjects were recruited from two bigger cohorts with previously reported data of scans at 6 months. The scans were acquired after injections of about 20 mCi MIBI at peak pharmacologic stress and at rest. The change of the perfusion abnormalities by both visual assessment and quantifications (Autoquant) at the baseline and 3 years follow up time are compared between exposed and control patients. Results: The exposed patients had more visual perfusion abnormality scores compared to control subjects (1.1 +/- 1.3 vs. 0.3 +/- 1.0; p=0.03). The indices of perfusion abnormality normalized in control subjects from baseline to follow up scans (p=0.05 for summed difference score and p=0.04 for summed stress score). The difference of the perfusion abnormalities between the exposed and unexposed subjects remained unchanged along the 3 years of follow up. Conclusion: The radiation induced myocardial perfusion abnormalities in patients with left breast cancer could cause permanent coronary disease over time.