Speckle tracking echocardiography (STE) or two-dimensional (2D) strain imaging is a novel ultrasound method to assess myocardial deformation. Peak systolic longitudinal strain (PSLS) of the basal septum (IVS) and the opposite lateral (LVFW) wall were measured in addition to standard echocardiography in 88 consecutive patients (pts) with obstructive hypertrophic cardiomyopathy (HOCM) who underwent a septal ablation procedure (PTSMA) and who were re-evaluated 12 ± 12 after months. At baseline, PSLS was substantially reduced both in basal regions. While PSLS remained unchanged in the basal IVS, i.e. the target region for PTSMA (baseline: −5.3 ± 4.1%; follow-up: −6.0 ± 4.3%; P = 0.06), it improved in the opposite LVFW (from −9.4 ± 4.7 to −12.4 ± 4.8%; P < 0.0001). Wall thickness decreased in both regions (Septum: from 20 ± 4 to 17 ± 4 mm; P < 0.0001; LV free wall: from 13 ± 2 to 12 ± 2 mm; P = 0.001). PSLS correlated significantly with wall thickness, both at baseline and at follow-up. NYHA functional class (from 2.9 ± 0.4 to 1.6 ± 0.6; P < 0.0001) and objective exercise capacity (from 96 ± 42 to 114 ± 42 W; P = 0.001) improved together with the reduction of outflow obstruction (LVOTO: from 62 ± 30 to 11 ± 19 mm Hg at rest, from 121 ± 26 to 43 ± 40 mm Hg with provocation; P < 0.0001). During the 12 months of observation, no patient had a severe adverse event. Regional myocardial deformation can be assessed quantitatively by STE. Reduction of LV afterload by elimination of the outflow gradient following a successful PTSMA with low doses of alcohol results in improvement of systolic lateral longitudinal function.