Septal reduction therapy (via alcohol septal ablation or surgical myomectomy) is indicated in patients with hypertrophic obstructive cardiomyopathy (HOCM) who have NYHA class III/IV symptoms despite maximal medical therapy. In 90% of patients with HOCM the target septal artery arises from the LAD or diagonal artery. In the remaining 10% of cases it may arise from the ramus, proximal circumflex, or posterolateral or posterior descending branches of the RCA. We present a case where alcohol septal ablation was initially performed on the first septal branch arising from the left anterior descending artery. Left ventricular outflow tract (LVOT) obstruction with symptoms recurred. Upon repeat angiography, a large septal branch in fact arose from the proximal intermediate (ramus) artery. Alcohol ablation of this branch achieved a sustained response. This case highlights that correctly identifying the most suitable septal perforating artery, in addition to myocardial contrast echocardiography, may improve response rates and overall outcomes for patients with hypertrophic obstructive cardiomyopathy.