Objectives The aim of this study was to evaluate the effects of alcohol septal ablation (ASA) on coronary blood flow in symptomatic hypertrophic obstructive cardiomyopathy (HOCM) using cardiac MR (CMR) coronary flow measurements. Background CMR flow mapping enables quantification of coronary blood flow in a noninvasive way. Both left ventricular outflow tract (LVOT) gradient reduction and myocardial scarring after ASA are expected to influence left anterior descending (LAD) coronary blood flow. Methods Cine, contrast-enhanced (CE) imaging and breath-hold CMR phase contrast velocity mapping were performed at baseline and 1 and 6 months after ASA in seven patients. Changes of coronary blood flow were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LVOT gradient reduction, and LV rate pressure product (LVRPP). Results A significant mass reduction was observed both in the target septal myocardium and in the total myocardium (both P < 0.01). Mean myocardial infarct size was 23 ± 12 g (range 7.3–41.6 g). LVRPP decreased from 13,268 ± 2,212 to 10,685 ± 3,918 at 1 month (P = 0.05) and 9,483 ± 2,496 mmHg beats/min at 6 months’ follow-up (P < 0.01). LAD coronary blood flow decreased from 100 ± 37 ml/min at baseline to 84 ± 54 ml/min (P = 0.09) at 1 month and 67 ± 33 ml/min at 6 months follow-up (P < 0.01). A significant correlation was found between the change in LVRPP and LAD coronary flow at 1 month follow-up (r = 0.83, P = 0.02). CE-infarct size tended to modulate the blood flow changes over time (P = 0.12); no correlation was observed between enzyme release, volume of ethanol or both septal and total mass reduction and coronary blood flow. Conclusion The reduction in coronary blood flow is primarily associated with diminished LV loading conditions, whereas the induction of metabolically inactive myocardial scar tissue by ASA did not significantly influence the changes in coronary blood flow.