Myocardial infarct (MI) size is a well-established prognostic marker but the association of serum markers with MI size, as measured by myocardial perfusion imaging (MPI), has not been well studied in patients with hypertrophic cardiomyopathy (HC) after alcohol septal ablation (ASA). Creatine kinase (CK), CK-MB, troponin I, and brain natriuretic peptide were measured before and at multiple points after ASA in patients with HC and were correlated with MI size measured by MPI. MPI at rest was performed in 54 patients with HC at a median of 2 days after ASA. CK, CK-MB, and troponin I increased after ASA to peak levels at 12 hours and their cumulative levels (area under the curve) showed significant correlation with size of MI by MPI (r = 0.544, 0.408, and 0.477, p <0.001, 0.003, and 0.001, respectively). The best marker was level of CK at 12 hours (r = 0.609, p <0.0001) after ASA. Brain natriuretic peptide level did not change significantly after ASA (p = 1.0) and only weakly correlated with MI size by MPI (r = 0.130, p = 0.007). In conclusion, CK, CK-MB, and troponin I measured at 12 hours, at peak, and as the area under the curve correlated well with infarct size, but CK level at 12 hours was the best marker. CK continues to be a useful marker of MI size despite the introduction of newer, more specific markers, especially when infarct onset is known with certainty as in patients with HC undergoing ASA.