Alcohol septal ablation (ASA) as a treatment for obstructive hypertrophic cardiomyopathy produces septal infarction. There is a concern that such infarcts could be detrimental. Changes in the size of these infarcts by serial perfusion testing have not been studied. We performed resting serial-gated single-photon emission computed tomographic myocardial perfusion imaging in 30 patients (age 51 ± 17 years, 57% were women) who had ASA between September 2003 and March 2007 before, 2 ± 0.8 days (early), and 8.4 ± 6.9 months (late) after ASA. Patients were also followed clinically and with serial 2-dimensional echocardiography. New York Heart Association class decreased from 3.50 ± 0.51 before to 1.14 ± 0.36 (p <0.0001) 3 months after ASA. The left ventricular (LV) outflow gradient (by Doppler echocardiography) decreased from 63 ± 32 mm Hg before to 28 ± 23 mm Hg after ASA (p <0.005). None of the patients had perfusion defects at rest before ASA. After ASA, perfusion defect size, involving the basal septum, decreased from 9.4 ± 5.8% early to 5.2 ± 4.2% of LV myocardium late after ASA (p <0.001). There were no changes in LV size and ejection fraction after ASA. In conclusion, ASA produces small basal ventricular septal infarcts (resting perfusion abnormality) involving <10% of the LV myocardium (including ventricular septum). There is a significant reduction in the perfusion abnormality late after ASA without an increase in LV outflow obstruction or recurrence of symptoms. © 2008 Elsevier Inc. All rights reserved.