Background: Regional heterogeneity of left ventricular (LV) hypertrophy may contribute to arrhythmic vulnerability in patients with hypertrophic cardiomyopathy (HCM). The aim of the present study was to investigate the relationship between LV wall thickness (LVWT) and microvolt T-wave alternans (TWA), a surrogate risk marker of ventricular tachyarrhythmias (VTAs). Methods and Results: A total of 157 consecutive HCM patients underwent 2-D echocardiography and TWA-exercise testing, and assessment of arrhythmic burden in a follow up of a median 3.7 years. VTAs were commoner in the non-negative groups (NN-TWA: n=72, TWA+ and indeterminate outcome; 29 events, P<0.02; TWA+: n=34; 14 events, P=0.01), than in the negative TWA group (n=85, 16 events). TWA+ patients were older (P<0.04) and had greater maximal LVWT and LV mass (P=0.02 and P=0.05, respectively), whereas NN-TWA linked only with increased LV mass (P=0.05). Regionally, the TWA+ group had greater inferior LVWT (P<0.05). TWA+ outcome positively correlated with maximal LVWT (r=0.2, P=0.05), and basal/equatorial/apical inferior LVWT (BA6: r=0.2, P=0.05 and EQ6: r=0.2 P=0.03, AP6: r=0.2, P=0.04). Multivariate analysis identified left atrium size, max LVWT and EQ6 with predictive association for TWA+ outcome. Conclusions: Positive and NN-TWA outcomes are associated with increased LV mass. Moreover, TWA+ is associated with maximal and regional LVWT in HCM patients at risk of arrhythmic events. The present findings support the complementary role of key regional LVWTs in a risk stratification model.  (Circ J 2010; 74: 1197 - 1204)